Neoplastic Stem Cells: Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Stem Cell Transplantation: The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types.Embryonic Stem Cells: Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.Adult Stem Cells: Cells with high proliferative and self renewal capacities derived from adults.Dietary Supplements: Products in capsule, tablet or liquid form that provide dietary ingredients, and that are intended to be taken by mouth to increase the intake of nutrients. Dietary supplements can include macronutrients, such as proteins, carbohydrates, and fats; and/or MICRONUTRIENTS, such as VITAMINS; MINERALS; and PHYTOCHEMICALS.Herb-Drug Interactions: The effect of herbs, other PLANTS, or PLANT EXTRACTS on the activity, metabolism, or toxicity of drugs.Vitamins: Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes.Caloric Restriction: Reduction in caloric intake without reduction in adequate nutrition. In experimental animals, caloric restriction has been shown to extend lifespan and enhance other physiological variables.Energy Transfer: The transfer of energy of a given form among different scales of motion. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed). It includes the transfer of kinetic energy and the transfer of chemical energy. The transfer of chemical energy from one molecule to another depends on proximity of molecules so it is often used as in techniques to measure distance such as the use of FORSTER RESONANCE ENERGY TRANSFER.National Academy of Sciences (U.S.): A United States organization of distinguished scientists and engineers established for the purpose of investigating and reporting upon any subject of art or science as requested by any department of government. The National Research Council organized by NAS serves as the principal operating agency to stimulate and support research.Platyhelminths: A phylum of acoelomate, bilaterally symmetrical flatworms, without a definite anus. It includes three classes: Cestoda, Turbellaria, and Trematoda.Turbellaria: A class of free-living freshwater flatworms of North America.Institute of Medicine (U.S.): Identifies, for study and analysis, important issues and problems that relate to health and medicine. The Institute initiates and conducts studies of national policy and planning for health care and health-related education and research; it also responds to requests from the federal government and other agencies for studies and advice.Planarians: Nonparasitic free-living flatworms of the class Turbellaria. The most common genera are Dugesia, formerly Planaria, which lives in water, and Bipalium, which lives on land. Geoplana occurs in South America and California.Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.IndianaCatalogs, LibraryCatalogs as Topic: Ordered compilations of item descriptions and sufficient information to afford access to them.Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Catalogs, UnionDatabases, Factual: Extensive collections, reputedly complete, of facts and data garnered from material of a specialized subject area and made available for analysis and application. The collection can be automated by various contemporary methods for retrieval. The concept should be differentiated from DATABASES, BIBLIOGRAPHIC which is restricted to collections of bibliographic references.Copyright: It is a form of protection provided by law. In the United States this protection is granted to authors of original works of authorship, including literary, dramatic, musical, artistic, and certain other intellectual works. This protection is available to both published and unpublished works. (from Circular of the United States Copyright Office, 6/30/2008)Pluripotent Stem Cells: Cells that can give rise to cells of the three different GERM LAYERS.American Heart Association: A voluntary organization concerned with the prevention and treatment of heart and vascular diseases.Heart Failure: A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.Heart: The hollow, muscular organ that maintains the circulation of the blood.Cardiology: The study of the heart, its physiology, and its functions.Congresses as Topic: Conferences, conventions or formal meetings usually attended by delegates representing a special field of interest.Stem Cell Niche: A particular zone of tissue composed of a specialized microenvironment where stem cells are retained in a undifferentiated, self-renewable state.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Rothmund-Thomson Syndrome: An autosomal recessive syndrome occurring principally in females, characterized by the presence of reticulated, atrophic, hyperpigmented, telangiectatic cutaneous plaques, often accompanied by juvenile cataracts, saddle nose, congenital bone defects, disturbances in the growth of HAIR; NAILS; and TEETH; and HYPOGONADISM.Diploidy: The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.RecQ Helicases: A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging.Cockayne Syndrome: A syndrome characterized by multiple system abnormalities including DWARFISM; PHOTOSENSITIVITY DISORDERS; PREMATURE AGING; and HEARING LOSS. It is caused by mutations of a number of autosomal recessive genes encoding proteins that involve transcriptional-coupled DNA REPAIR processes. Cockayne syndrome is classified by the severity and age of onset. Type I (classical; CSA) is early childhood onset in the second year of life; type II (congenital; CSB) is early onset at birth with severe symptoms; type III (xeroderma pigmentosum; XP) is late childhood onset with mild symptoms.Werner Syndrome: An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease.BaltimorePrion Diseases: A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83)PrPC Proteins: Normal cellular isoform of prion proteins (PRIONS) encoded by a chromosomal gene and found in normal and scrapie-infected brain tissue, and other normal tissue. PrPC are protease-sensitive proteins whose function is unknown. Posttranslational modification of PrPC into PrPSC leads to infectivity.Prions: Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL.Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism.PrPSc Proteins: Abnormal isoform of prion proteins (PRIONS) resulting from a posttranslational modification of the cellular prion protein (PRPC PROTEINS). PrPSc are disease-specific proteins seen in certain human and animal neurodegenerative diseases (PRION DISEASES).Scrapie: A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called PRIONS.Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (1/4087)

The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16(Ink4a), suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by +info)

Postnatal growth failure, short life span, and early onset of cellular senescence and subsequent immortalization in mice lacking the xeroderma pigmentosum group G gene. (2/4087)

The xeroderma pigmentosum group G (XP-G) gene (XPG) encodes a structure-specific DNA endonuclease that functions in nucleotide excision repair (NER). XP-G patients show various symptoms, ranging from mild cutaneous abnormalities to severe dermatological impairments. In some cases, patients exhibit growth failure and life-shortening and neurological dysfunctions, which are characteristics of Cockayne syndrome (CS). The known XPG protein function as the 3' nuclease in NER, however, cannot explain the development of CS in certain XP-G patients. To gain an insight into the functions of the XPG protein, we have generated and examined mice lacking xpg (the mouse counterpart of the human XPG gene) alleles. The xpg-deficient mice exhibited postnatal growth failure and underwent premature death. Since XPA-deficient mice, which are totally defective in NER, do not show such symptoms, our data indicate that XPG performs an additional function(s) besides its role in NER. Our in vitro studies showed that primary embryonic fibroblasts isolated from the xpg-deficient mice underwent premature senescence and exhibited the early onset of immortalization and accumulation of p53.  (+info)

Analysis of genomic integrity and p53-dependent G1 checkpoint in telomerase-induced extended-life-span human fibroblasts. (3/4087)

Life span determination in normal human cells may be regulated by nucleoprotein structures called telomeres, the physical ends of eukaryotic chromosomes. Telomeres have been shown to be essential for chromosome stability and function and to shorten with each cell division in normal human cells in culture and with age in vivo. Reversal of telomere shortening by the forced expression of telomerase in normal cells has been shown to elongate telomeres and extend the replicative life span (H. Vaziri and S. Benchimol, Curr. Biol. 8:279-282, 1998; A. G. Bodnar et al., Science 279:349-352, 1998). Extension of the life span as a consequence of the functional inactivation of p53 is frequently associated with loss of genomic stability. Analysis of telomerase-induced extended-life-span fibroblast (TIELF) cells by G banding and spectral karyotyping indicated that forced extension of the life span by telomerase led to the transient formation of aberrant structures, which were subsequently resolved in higher passages. However, the p53-dependent G1 checkpoint was intact as assessed by functional activation of p53 protein in response to ionizing radiation and subsequent p53-mediated induction of p21(Waf1/Cip1/Sdi1). TIELF cells were not tumorigenic and had a normal DNA strand break rejoining activity and normal radiosensitivity in response to ionizing radiation.  (+info)

Downregulation of metallothionein-IIA expression occurs at immortalization. (4/4087)

Metallothioneins (MTs) may modulate a variety of cellular processes by regulating the activity of zinc-binding proteins. These proteins have been implicated in cell growth regulation, and their expression is abnormal in some tumors. In particular, MT-IIA is expressed 27-fold less in human colorectal tumors and tumor cell lines compared with normal tissue (Zhang et al., 1997). Here we demonstrate that MT-IIA downregulation occurs when human cells become immortal, a key event in tumorigenesis. After immortalization MT-IIA expression remains inducible but the basal activity of the MT-IIA promoter is decreased. MT-IIA downregulation at immortalization is one of the most common immortalization-related changes identified to date, suggesting that MT-IIA has a role in this process.  (+info)

A telomere-independent senescence mechanism is the sole barrier to Syrian hamster cell immortalization. (5/4087)

Reactivation of telomerase and stabilization of telomeres occur simultaneously during human cell immortalization in vitro and the vast majority of human cancers possess high levels of telomerase activity. Telomerase repression in human somatic cells may therefore have evolved as a powerful resistance mechanism against immortalization, clonal evolution and malignant progression. The comparative ease with which rodent cells immortalize in vitro suggests that they have less stringent controls over replicative senescence than human cells. Here, we report that Syrian hamster dermal fibroblasts possess substantial levels of telomerase activity throughout their culture life-span, even after growth arrest in senescence. In our studies, telomerase was also detected in uncultured newborn hamster skin, in several adult tissues, and in cultured fibroblasts induced to enter the post-mitotic state irreversibly by serum withdrawal. Transfection of near-senescent dermal fibroblasts with a selectable plasmid vector expressing the SV40 T-antigen gene resulted in high-frequency single-step immortalization without the crisis typically observed during the immortalization of human cells. Collectively, these data provide an explanation for the increased susceptibility of rodent cells to immortalization (and malignant transformation) compared with their human equivalents, and provide evidence for a novel, growth factor-sensitive, mammalian senescence mechanism unrelated to telomere maintenance.  (+info)

Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2'-deoxycytidine treatment induces a senescence-like state. (6/4087)

We have previously reported that a set of oral squamous cell carcinoma lines express specifically elevated cdk6 activity. One of the cell lines, SCC4, contains a cdk6 amplification and expresses functional p16ink4a, the other cell lines express undetectable levels of p16ink4a, despite a lack of coding-region mutations. Two of the cell lines, SCC15 and SCC40 have a hypermethylated p16ink4A promoter and a third cell line, SCC9, has a mutation in the p16ink4a promoter. Using the demethylation agent 5-aza-2'-deoxycytidine, we showed that the p16ink4a protein was re-expressed after a 5-day treatment with this chemical. One cell line, SCC15 expressed high levels of p16ink4a. In this line, cdk6 activity was decreased after 5-aza-2'deoxycytidine treatment, and the hypophosphorylated, growth suppressive form of the retinoblastoma tumor suppressor protein pRB was detected. Expression of p16ink4a persisted, even after the drug was removed and the cells expressed senescence-associated beta-galactosidase activity. Ectopic expression of p16ink4a with a recombinant retrovirus in this cell line also induced a similar senescence-like phenotype. Hence, it was possible to restore a functional pRB pathway in an oral squamous cell carcinoma line by inducing re-expression of endogenous p16ink4a in response to treatment with a demethylating agent.  (+info)

The synaptophysin-synaptobrevin complex: a hallmark of synaptic vesicle maturation. (7/4087)

Exocytosis of synaptic vesicles requires the formation of a fusion complex consisting of the synaptic vesicle protein synaptobrevin (vesicle-associated membrane protein, or VAMP) and the plasma membrane proteins syntaxin and soluble synaptosomal-associated protein of 25 kDa (or SNAP 25). In search of mechanisms that regulate the assembly of the fusion complex, it was found that synaptobrevin also binds to the vesicle protein synaptophysin and that synaptophysin-bound synaptobrevin cannot enter the fusion complex. Using a combination of immunoprecipitation, cross-linking, and in vitro interaction experiments, we report here that the synaptophysin-synaptobrevin complex is upregulated during neuronal development. In embryonic rat brain, the complex is not detectable, although synaptophysin and synaptobrevin are expressed and are localized to the same nerve terminals and to the same pool of vesicles. In contrast, the ability of synaptobrevin to participate in the fusion complex is detectable as early as embryonic day 14. The binding of synaptoporin, a closely related homolog of synaptophysin, to synaptobrevin changes in a similar manner during development. Recombinant synaptobrevin binds to synaptophysin derived from adult brain extracts but not to that derived from embryonic brain extracts. Furthermore, the soluble cytosol fraction of adult, but not of embryonic, synaptosomes contains a protein that induces synaptophysin-synaptobrevin complex formation in embryonic vesicle fractions. We conclude that complex formation is regulated during development and is mediated by a posttranslational modification of synaptophysin. Furthermore, we propose that the synaptophysin-synaptobrevin complex is not essential for exocytosis but rather provides a reserve pool of synaptobrevin for exocytosis that can be readily recruited during periods of high synaptic activity.  (+info)

Intracytoplasmic sperm injection after follicle stimulation with highly purified human follicle-stimulating hormone compared with human menopausal gonadotropin. (8/4087)

PURPOSE: Our purpose was to compare oocyte nuclear maturation and embryo quality after pituitary down-regulation and ovarian stimulation with highly purified follicle-stimulating hormone (FSH) or human menopausal gonadotropin (HMG). METHODS: Fifty-five patients 37 years of age or younger who were undergoing in vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) were evaluated retrospectively. In all cases, male factor was the only indication for treatment, with no female-related factors identified. Following pituitary down-regulation, patients were stimulated with hMG (n = 20) or highly purified FSH (n = 35). Main outcome measures included ovarian response to stimulation, oocyte maturity, and ICSI fertilization results. Secondary outcome measures included pregnancy rates and outcome. RESULTS: The ovarian response to stimulation was similar for the two groups, as were the percentage of metaphase II oocytes, fertilization and cleavage rates, and number and quality of transferred and cryopreserved embryos. Cycle outcome was comparable. CONCLUSIONS: In normogonadotropic subjects, monocomponent therapy with highly purified FSH is as effective as hMG in stimulating ovarian follicular development, synchronization of oocyte maturation, and IVF-ICSI outcome. Our findings support the conclusion that the luteinizing hormone component in the stimulation protocol is unnecessary.  (+info)

From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes - Age-associated diseases;Cell senescence;Differential expression;Senescence-associated secretory phenotypes (SASP);
Communication between cells is quintessential for biological function and cellular homeostasis. Membrane-bound extracellular vesicles known as exosomes play pivotal roles in mediating intercellular communication in tumor microenvironments. These vesicles and exosomes carry and transfer biomolecules such as proteins, lipids and nucleic acids. Here we focus on exosomes secreted from senescent cells. Cellular senescence can alter the microenvironment and influence neighbouring cells via the senescence-associated secretory phenotype (SASP), which consists of factors such as cytokines, chemokines, matrix proteases and growth factors. This review focuses on exosomes as emerging SASP components that can confer pro-tumorigenic effects in pre-malignant recipient cells. This is in addition to their role in carrying SASP factors. Transfer of such exosomal components may potentially lead to cell proliferation, inflammation and chromosomal instability, and consequently cancer initiation. Senescent cells are ...
Hematologic malignancies are typically associated with leukemogenic fusion proteins, which are required to maintain the oncogenic state. Previous studies have shown that certain oncogenes that promote solid tumors, such as RAS and BRAF, can induce senescence in primary cells, which is thought to provide a barrier to tumorigenesis. In these cases, the activated oncogene elicits a DNA damage response (DDR), which is essential for the senescence program. Here we show that 3 leukemogenic fusion proteins, BCR-ABL, CBFB-MYH11, and RUNX1-ETO, can induce senescence in primary fibroblasts and hematopoietic progenitors. Unexpectedly, we find that senescence induction by BCR-ABL and CBFB-MYH11 occurs through a DDR-independent pathway, whereas RUNX1-ETO induces senescence in a DDR-dependent manner. All 3 fusion proteins activate the p38 MAPK pathway, which is required for senescence induction. Our results reveal diverse pathways for oncogene-induced senescence and further suggest that leukemias harbor genetic or
Can regular aerobic exercise diminish the damaging effects of aging on the vascular system by improving the health of vascular endothelial cells? In this insightful podcast, Associate Editor Nancy Kanagy interviews lead author Matthew Rossman (University of Colorado Boulder) and content expert Raymond Migrino (Phoenix VA Health Care System) about the work by Rossman et al focusing on age-related changes in endothelial cell senescence and associated changes in endothelial cell function that occurs with normal, healthy aging. Habitual exercise has been shown to reduce age-related phenotypic changes such as increased arterial stiffness and reduced endothelial cell function. Did Rossman and colleagues find that regular aerobic exercise in older adults ameliorated increases in endothelial cell senescence? Listen and learn more.. Matthew J. Rossman, Rachelle E. Kaplon, Sierra D. Hill, Molly N. McNamara, Jessica R. Santos-Parker, Gary L. Pierce, Douglas R. Seals, Anthony J. Donato Endothelial cell ...
TY - JOUR. T1 - Oxidative stress-induced senescence markedly increases disc cell bioenergetics. AU - Patil, Prashanti. AU - Falabella, Micol. AU - Saeed, Amal. AU - Lee, Dayeong. AU - Kaufman, Brett. AU - Shiva, Sruti. AU - Croix, Claudette St. AU - Van Houten, Ben. AU - Niedernhofer, Laura J.. AU - Robbins, Paul D.. AU - Lee, Joon. AU - Gwendolyn, Sowa. AU - Vo, Nam V.. PY - 2019/6. Y1 - 2019/6. N2 - Cellular senescence is a phenotype characterized by irreversible growth arrest, chronic elevated secretion of proinflammatory cytokines and matrix proteases, a phenomenon known as senescence-associated secretory phenotype (SASP). Biomarkers of cellular senescence have been shown to increase with age and degeneration of human disc tissue. Senescent disc cells in culture recapitulate features associated with age-related disc degeneration, including increased secretion of proinflammatory cytokines, matrix proteases, and fragmentation of matrix proteins. However, little is known of the metabolic ...
Senescent cells are cells that no longer divide. These cells acquire a large and flat cellular appearance, decrease contacts with other cells, and increase adhesion to the extracellular matrix. In normal replicative senescence, the cell simply enters senescence after a certain number of replications. However, stress-induced senescence causes cells to initiate senescence prematurely due to a variety of stresses. In fact, some hypothesize that the senescence program originally evolved as an antiviral mechanism. This burgeoning field may also yield other important clues about the cellular biology of aging. Molecularly, the cellular senescence program activates p53 and pRb signaling, leading to withdrawal from the cell cycle. Stress pathways that may cause cellular senescence include DNA damage, oxidative stress, interferon-related responses, and signaling via either insulin growth factors (IGF) or mitogen activated protein kinases (MAPK). Due to cellular senescence activation in early stage cancers ...
Pathological angiogenesis is the hallmark of diseases such as cancer and retinopathies. Although tissue hypoxia and inflammation are recognized as central drivers of vessel growth, relatively little is known about the process that bridges the two. In a mouse model of ischemic retinopathy, we found that hypoxic regions of the retina showed only modest rates of apoptosis despite severely compromised metabolic supply. Using transcriptomic analysis and inducible loss-of-function genetics, we demonstrated that ischemic retinal cells instead engage the endoplasmic reticulum stress inositol-requiring enzyme 1α (IRE1α) pathway that, through its endoribonuclease activity, induces a state of senescence in which cells adopt a senescence-associated secretory phenotype (SASP). We also detected SASP-associated cytokines (plasminogen activator inhibitor 1, interleukin-6, interleukin-8, and vascular endothelial growth factor) in the vitreous humor of patients suffering from proliferative diabetic retinopathy. ...
Supplementary MaterialsData?S1 Foam cell-derived 4-hydroxynonenal induces endothelial cell senescence inside a TXNIP-dependent manner. was triggered by 4-hydroalkenals, such as 4-HNE. Pharmacological interventions supported the involvement of the 4-HNE-PPAR axis in the induction of TXNIP and VEC senescence. The association of TXNIP with VEC senescence was further supported by immunofluorescent staining of human being carotid plaques in which the manifestation of both TXNIP and p21 was augmented in endothelial cells. Collectively, order AZD6738 these findings suggest that foam cell-released 4-HNE activates PPAR in VEC, leading to improved TXNIP manifestation and consequently to senescence. by incubating nLDL under sterile conditions with 10?M copper chloride (24?hrs, at 37C), in the absence of antioxidant safety. The oxidative reaction was halted by addition of 1 1?mg/ml EDTA and after extensive dialysis against PBS, pH 7.4, 4C, oxLDL was stored at 4C, under sterile conditions. The copper-OxLDL ...
1. Bastonini E, Kovacs D, Picardo M. Skin pigmentation and pigmentary disorders: Focus on epidermal/dermal cross-talk. Ann Dermatol. 2016;28:279-89 2. Kim M, Han JH, Kim JH, Park TJ, Kang HY. Secreted frizzled-related protein 2 (sFRP2) functions as a melanogenic stimulator; The role of sFRP2 in UV-induced hyperpigmentary disorders. J Invest Dermatol. 2016;136:236-44 3. Coppé JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: The dark side of tumor suppression. Annu Rev Pathol. 2010;5:99-118 4. Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL. Cellular senescence and the senescent secretory phenotype: Therapeutic opportunities. J Clin Invest. 2013;123:966-72 5. Kim YH, Choi YW, Lee JH, Soh EY, Kim JH, Park TJ. Senescent tumor cells lead the collective invasion in thyroid cancer. Nat Commun. 2017;8:15208 6. Mine S, Fortunel NO, Pageon H, Asselineau D. Aging alters functionally human dermal papillary fibroblasts but not reticular fibroblasts: A new view ...
The Scientific World Journal is a peer-reviewed, Open Access journal that publishes original research, reviews, and clinical studies covering a wide range of subjects in science, technology, and medicine. The journal is divided into 81 subject areas.
The results of this study demonstrated that statins inhibit oxidative stress-induced endothelial senescence and that, subsequently, upregulation of SIRT1 plays a critical role in prevention of senescence through Akt pathway.. The mechanisms by which statins stimulate the expression and activation of eNOS appear to involve the geranylgeranyl pathway, because mevalonate, GGPP, and FPP reversed the inhibitory effect of statins on senescence. It is well known that inhibition of geranylgeranylation leads to inactivation of Rho kinase. However, pharmacological inhibitors of Rho kinase did not affect endothelial senescence, which indicated that the inhibitory effect of statins on senescence was not mediated by inhibition of Rho kinase. Moreover, treatment with statins increased the phosphorylation of Akt at Ser473. Treatment with Akt siRNA or LY294002, which inhibited phosphorylation of Akt at Ser473, abrogated the eNOS activation and antisenescent property of atorvastatin. These results demonstrate ...
Cellular senescence is a complex phenotype observed in diverse tissues at distinct developmental stages. In adults, senescence likely acts to irreversibly prevent proliferation of damaged cells. Senescent cells appear during chronological aging, aberrant oncogene expression, and exposure to DNA damaging agents. Expression of the tumor suppressor p16INK4a increases with age in numerous mouse and human tissues and, thus, considered a reliable marker. Exposure to ionizing radiation (IR) leads to delayed increase in p16INK4a expression in mice tissues and cancer-treated patients Senescent cells accumulate in tissues and secrete a range of cytokines, chemokines, and proteases known as the senescence-associated secretory phenotype (SASP). Why senescent cells accumulate in vivo remains unclear. One theory suggests senescence accumulates with a decline in immune functions with age. While senescent cells support wound healing, accumulation of senescent cells also appears to contribute to tumor growth and ...
Chronic obstructive pulmonary disease (COPD) is a highly prevalent and devastating condition for which no curative treatment is available. Exaggerated lung cell senescence may be a major pathogenic factor. Here, we investigated the potential role for mTOR signaling in lung cell senescence and alterations in COPD using lung tissue and derived cultured cells from patients with COPD and from age- and sex-matched control smokers. Cell senescence in COPD was linked to mTOR activation, and mTOR inhibition by low-dose rapamycin prevented cell senescence and inhibited the proinflammatory senescence-associated secretory phenotype. To explore whether mTOR activation was a causal pathogenic factor, we developed transgenic mice exhibiting mTOR overactivity in lung vascular cells or alveolar epithelial cells. In this model, mTOR activation was sufficient to induce lung cell senescence and to mimic COPD lung alterations, with the rapid development of lung emphysema, pulmonary hypertension, and inflammation. ...
Cellular senescence is a fundamental cell fate playing significant and complex roles during tumorigenesis and natural aging process. However, the molecular determinants distinguishing senescence from other temporary and permanent cell-cycle arrest states such as quiescence and post-mitotic state and the specified mechanisms underlying cell-fate decisions towards senescence versus cell death in response to cellular stress stimuli remain less understood. In our studies, we aimed to employ multi-omics approaches to deepen our understanding of cellular senescence, in particular, regarding the specific molecular determinants distinguishing cellular senescence from other non-dividing cell fates. Notably, one of the most prominent features of cellular senescence differing from other non-dividing cell fates is the increased expression of senescence-associated beta-galactosidase. Because 5-Dodecanoylaminofluorescein Di-β-D-Galactopyranoside (C12FDG) is known as the substrate catalyzed by ...
Full Text - Vascular calcification is commonly seen in elderly people, though it can also appear in middle-aged subjects affected by premature vascular aging. The aim of this work is to test the involvement of microvesicles (MVs) produced by senescent endothelial cells (EC) and from plasma of elderly people in vascular calcification. The present work shows that MVs produced by senescent cultured ECs, plus those found in the plasma of elderly subjects, promote calcification in vascular smooth muscle cells. Only MVs from senescent ECs, and from elderly subjects plasma, induced calcification. This ability correlated with these types of MVs carriage of: a) increased quantities of annexins (which might act as nucleation sites for calcification), b) increased quantities of bone-morphogenic protein, and c) larger Ca contents. The MVs of senescent, cultured ECs, and those present in the plasma of elderly subjects, promote vascular calcification. The present results provide mechanistic insights into the
Even under conditions where the immune system cannot kill the cancer, the two cytokines interferon (IFN) and tumor necrosis factor (TNF), may drive cancers into senescence. Thus, senescence induction causes a state, where ‚the cancer sleeps well controlled in his host. This was first shown in an islet cancer of the pancreas (1, 4).. The same two cytokines, IFN and TNF, can drive a large number of mouse and human cancer cells into senescence. Clinically, this has two major consequences: Immune-induced senescence (figure 1) is obviously a physiological mechanism that contributes to the natural cancer control in humans (1). On the other side, recent data from cancer immune therapy suggest that the therapy is primarily efficient under conditions where the immune therapy causes permanent growth arrest of the metastases (8, 9).. Two mediators that are long known in cancer and infection immunology turn into the focus: interferon (IFN) and tumor necrosis factor (TNF). Many clinicians and researchers ...
In this work, we found that a MT1‐MMP‐dependent signaling between a defective ECM and the cell nucleus activates a senescence response that could explain some of the phenotypes caused by the loss of Mmp14 in mouse. This senescence process involves p16INK4a and p21CIP1/WAF1 and is also characterized by a series of archetypal senescent features, such as the presence of marked nuclear envelope abnormalities, the occurrence of a reduced proliferative potential, the induction of a chronic DNA damage response, and the triggering of a senescence‐associated secretory phenotype which involves the production of several inflammatory factors. We also show that this senescence program can be partially reversed by interventions on retinoid receptor signaling pathways, as demonstrated by the fact that treatment with ATRA increases life span and restores some of the phenotypic alterations observed in Mmp14‐deficient mice.. Interestingly, most molecular and cellular features observed in Mmp14−/− mice ...
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Loss of MDM2 can trigger senescence in WD/DDLS(A) The indicated cells were transduced with two different MDM2 knockdown lentiviral vectors (M376 or M380) or a s
Cellular senescence is a cell fate program that entails essentially irreversible proliferative arrest in response to damage signals. Tumor necrosis factor-alpha (TNFα), an important pro-inflammatory cytokine secreted by some types of senescent cells, can induce senescence in mouse and human cells. However, downstream signaling pathways linking TNFα-related inflammation to senescence are not fully characterized. Using human umbilical vein endothelial cells (HUVECs) as a model, we show that TNFα induces permanent growth arrest and increases p21CIP1, p16INK4A, and SA-β-gal, accompanied by persistent DNA damage and ROS production. By gene expression profiling, we identified the crucial involvement of inflammatory and JAK/STAT pathways in TNFα-mediated senescence. We found that TNFα activates a STAT-dependent autocrine loop that sustains cytokine secretion and an interferon signature to lock cells into senescence. Furthermore, we show STAT1/3 activation is necessary for cytokine and ROS production
Rationale: Uncontrolled growth of abdominal aortic aneurysms (AAAs) is a life-threatening vascular disease without an effective pharmaceutical treatment. AAA incidence dramatically increases with advancing age in men. However, the molecular mechanisms by which aging predisposes individuals to AAAs remain unknown. Objective: In this study, we investigated the role of Sirtuin 1 (SIRT1), a class Ⅲ histone deacetylase, in AAA formation and the underlying mechanisms linking vascular senescence and inflammation. Methods and Results: The expression and activity of SIRT1 were significantly decreased in human AAA samples. SIRT1 in vascular smooth muscle cells (VSMCs) was remarkably downregulated in the suprarenal aortas of aged mice, in which AAAs induced by Ang II infusion were significantly elevated. Moreover, VSMC-specific knockout of SIRT1 accelerated Ang II-induced formation and rupture of AAAs and AAA-related pathological changes, whereas VSMC-specific overexpression of SIRT1 suppressed Ang ...
Cellular senescence is the phenomenon by which normal ploid cells cease to divide. In culture, fibroblasts can reach a maximum of 50 cell divisions before becoming senescent. This phenomenon is known as "replicative senescence", or the Hayflick limit. Replicative senescence is the result of telomere shortening that ultimately triggers a DNA damage response. Cells can also be induced to senesce via DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes and cell-cell fusion, independent of telomere length. As such, cellular senescence represents a change in "cell state" rather than a cell becoming "aged" as the name misleadingly suggests. Nonetheless, the number of senescent cells in tissues rises substantially during normal aging. Although senescent cells can no longer replicate, they remain metabolically active and commonly adopt an immunogenic phenotype consisting of a pro-inflammatory secretome, the up-regulation of immune ligands, a pro-survival response, ...
Cellular senescence is an irreversible state of terminal growth arrest that requires functional p53. Acting to block tumor formation, induction of senescence has also been demonstrated to contribute to tumor clearance via the immune system following p53 reactivation.1, 2 The Hdm2-antagonist, Nutlin-3a, has been shown to reactivate p53 and induce a quiescent state in various cancer cell lines,3, 4 similar to the G1 arrest observed upon RNAi targeting of Hdm2 in MCF7 breast cancer.5 In the present study we show that HdmX, a negative regulator of p53, impacts the senescence pathway. Specifically, overexpression of HdmX blocks Ras mediated senescence in primary human fibroblasts. The interaction of HdmX with p53 and the re-localization of HdmX to the nucleus through Hdm2 association appear to be required for this activity. Furthermore, inhibiting HdmX in prostate adenocarcinoma cells expressing wild-type p53, mutant Ras and high levels of HdmX induced cellular senescence as measured by an increase in
Our studies reveal that the fundamental architecture of the genome undergoes profound alterations during replicative cellular senescence. One consequence is an overall closing of chromatin in euchromatic gene-rich regions, as evidenced by decreased FAIRE enrichment and associated dampening of gene activity, although some specific genes oppose this trend and become expressed at higher levels in senescent cells. Another, somewhat paradoxical trend, is an overall relative opening of chromatin in mostly heterochromatic gene-poor regions, as evidenced by increased FAIRE enrichment. The latter is associated with increased transcription of transposable elements, culminating in active transposition, as evidenced by an increase in copy number of L1 elements.. Telomere dysfunction drives a state of persistent DNA damage, which chronically activates the ATM and p53 pathways, leading to the cell cycle arrest that is the hallmark of senescence. Many forms of oncogene-induced senescence have also been ...
In culturing normal diploid cells, senescence may either happen naturally, in the form of replicative senescence, or it may be a consequence of external challenges such as oxidative stress. Here we present a comparative analysis aimed at reconstruction of molecular cascades specific for replicative (RS) and stressinduced senescence (SIPS) in human fibroblasts. An involvement of caspase-3/keratin-18 pathway and serine/threonine kinase Aurora A/ MDM2 pathway was shared between RS and SIPS. Moreover, stromelysin/MMP3 and N-acetylglucosaminyltransferase enzyme MGAT1, which initiates the synthesis of hybrid and complex Nglycans, were identified as key orchestrating components in RS and SIPS, respectively. In RS only, Aurora-B driven cell cycle signaling was deregulated in concert with the suppression of anabolic branches of the fatty acids and estrogen metabolism. In SIPS, Aurora-B signaling is deprioritized, and the synthetic branches of cholesterol metabolism are upregulated, rather than downregulated.
The characteristic limited reproductive life-span of normal human fibroblasts in culture is due to a steadily decreasing fraction of cells able to proliferate in the standard rich growth media. We have observed that restricting the growth factor supply to old cells for variable lengths of time in culture increases the fraction of cells that can enter S-phase; although these cells do not go on to divide. Thus, it seems that there is a transient phase between the proliferating state and the irreversibly post-mitotic, senescent state. Perhaps a quiescent-G0 state, which can be maintained in the presence of growth factors, is a stage on the pathway to mortalization and senescence. ...
Produced by senescent cells, the senescence-associated secretory phenotype (SASP) is a potential driver of age-related dysfunction. We tested whether circulating concentrations of SASP proteins reflect age and medical risk in humans. We first screened senescent endothelial cells, fibroblasts, preadipocytes, epithelial cells, and myoblasts to identify candidates for human profiling. We then tested associations between circulating SASP proteins and clinical data from individuals throughout the life span and older adults undergoing surgery for prevalent but distinct age-related diseases. A community-based sample of people aged 20-90 years (retrospective cross-sectional) was studied to test associations between circulating SASP factors and chronological age. A subset of this cohort aged 60-90 years and separate cohorts of older adults undergoing surgery for severe aortic stenosis (prospective longitudinal) or ovarian cancer (prospective case-control) were studied to assess relationships between ...
Over half a century ago, Hayflick and Moorhead demonstrated that primary human cells in culture have a limited capacity for replication [1]. After undergoing a finite number of divisions, these cells entered into a permanent cell cycle arrest, subsequently termed replicative or cellular senescence. They hypothesized that cellular senescence was a model‐in‐miniature of processes leading to organismal aging. They also noted that cancer cells divided indefinitely in culture, suggesting a role for replicative senescence in preventing cancer.. The intracellular signals that drive senescence remained obscure until the discovery of telomere erosion and telomerase. Telomeres are repetitive DNA sequences that comprise the ends of many linear chromosomes and protect them from degradation and recombination. Telomeres erode with each cell division due to the biochemical nature of DNA replication: the use of RNA‐based priming of the lagging strand and unidirectionality of DNA polymerases. Thus, ...
Premature or drug-induced senescence is a main cellular response to chemotherapy in stable tumors. results of Wip1 may become credited to its capability to dephosphorylate p53 at Ser15 and to lessen DNA harm response. Nevertheless, we also uncover a regulatory path whereby reductions of g53 Ser15 phosphorylation can be connected with improved phosphorylation at Ser46, improved g53 proteins amounts, and induction of Noxa appearance. On the entire, our data indicate that down-regulation of Wip1 appearance during premature senescence takes on a pivotal part in controlling many g53-reliant elements of the senescent phenotype. and and and and and and data not really demonstrated), an impact most likely attributable to a selection against Wip1-articulating senescent cells. Remarkably, under the circumstances utilized for regular distribution of the cells, in the lack of senescence induction, cells maintain a fairly steady level of FLAG-Wip1 appearance. 3 FIGURE. Cell routine distribution in senescent ...
Endothelial cell senescence is closely related to the occurrence of cardiovascular diseases and microRNAs (miRNAs/miRs) are considered as therapeutic targets for cardiovascular disease. The current study aimed to investigate the role of miR‑20b in the senescence process of endothelial cells and its underlying mechanism. Cell viability, proportion of senescent cells and the cell cycle were respectively determined by Cell Counting Kit‑8, SA‑β‑galactosidase and flow cytometry. The relative expressions of mRNA and protein were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The possible target genes and binding sites of miR‑20b were predicted using Targetscan and further verified by dual luciferase reporter assay. The present study found that H2O2 inhibited cell viability, caused cell cycle arrest in G1 phase, decreased miR‑20b level and induced cell senescence. Moreover, high expression of miR‑20b promoted cell viability ...
TY - JOUR. T1 - PAI-1 contributes to homocysteine-induced cellular senescence. AU - Sun, Tianjiao. AU - Ghosh, Asish K.. AU - Eren, Mesut. AU - Miyata, Toshio. AU - Vaughan, Douglas E.. PY - 2019/12. Y1 - 2019/12. N2 - Cellular Senescence is associated with organismal aging and related pathologies. Previously, we reported that plasminogen activator inhibitor-1 (PAI-1) is an essential mediator of senescence and a potential therapeutic target for preventing aging-related pathologies. In this study, we investigate the efficacies of PAI-1 inhibitors in both in vitro and in vivo models of homocysteine (Hcy)-induced cardiovascular aging. Elevated Hcy, a known risk factor of cardiovascular diseases, induces endothelial senescence as evidenced by increased senescence-associated β-Gal positivity (SA-β-Gal), flattened cellular morphology, and cylindrical appearance of cellular nuclei. Importantly, inhibition of PAI-1 by small molecule inhibitors reduces the number of SA-β-Gal positive cells, normalizes ...
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The tumor suppressor p16INK4a is a potent mediator of cell cycle arrest in transient expression studies, is induced in senescing cells, and can impose morphological features of senescence. Nonetheless, it is unclear whether p16INK4a can block cell proliferation irreversibly. We explored this issue u …
The exact mechanisms that connect the mind to the cell are unknown. Although it is well accepted that cell senescence can include stress-induced processes, psychological stress has not yet been considered as part of the stress pathway. The current findings suggest that stress-induced premature senescence in people might be influenced by chronic or perceived life stress. Psychological stress could affect cell aging through at least three nonmutually exclusive pathways: immune cell function or distribution, oxidative stress, or telomerase activity. We considered whether stress might have decreased naïve T cells and increased memory T cells [which have shorter telomere length (22)], but the data did not support this (Table 2, which is published as supporting information on the PNAS web site). Second, stress could potentially lead to oxidative stress by means of chronic activation of the autonomic and neuroendocrine stress responses. Although this hypothesis has never been tested in vivo, the ...
The p16INK4a cyclin-dependent kinase inhibitor is implicated in replicative senescence, the state of permanent growth arrest provoked by cumulative cell divisions or as a response to constitutive Ras-Raf-MEK signalling in somatic cells. Some contribution to senescence presumably underlies the importance of p16INK4a as a tumour suppressor but the mechanisms regulating its expression in these different contexts remain unknown. Here we demonstrate a role for the Ets1 and Ets2 transcription factors based on their ability to activate the p16INK4a promoter through an ETS-binding site and their patterns of expression during the lifespan of human diploid fibroblasts. The induction of p16INK4a by Ets2, which is abundant in young human diploid fibroblasts, is potentiated by signalling through the Ras-Raf-MEK kinase cascade and inhibited by a direct interaction with the helix-loop-helix protein Id1 (ref. 11). In senescent cells, where the Ets2 levels and MEK signalling decline, the marked increase in ...
Our study provides a method to rapidly screen putative S6K substrates by direct in vivo labelling. Quantitative phospho‐proteomic studies have recently led to the deep and high‐quality coverage of phosphopeptides whose abundance varies with perturbations in mTOR signalling (Moritz et al, 2010; Hsu et al, 2011; Yu et al, 2011; Robitaille et al, 2013). Strikingly, the phosphorylation of approximately 4% of human gene products is under control of the mTOR pathway. The phosphopeptides include direct mTOR substrates but also proteins whose phosphorylation is controlled by kinases and phosphatases downstream of mTOR. This information, in combination with in silico searches for Ser/Thr sites surrounded by basic residues, provides a powerful tool to interrogate the mTOR phospho‐proteome and reveals a subset of S6K direct substrates using an analogue‐specific mutant kinase. In this initial study, out of ten putative candidates, three proteins are reliably phosphorylated by AS‐S6K1: Cux1 is a ...
Background Previous work has demonstrated YPEL3 to be a growth-suppressive protein that acts through a pathway of cellular senescence. We set out to determine whether human colon tumors demonstrated downregulation of YPEL3. Methods We collected colon tumor samples with matched normal control samples and analyzed them forYPEL3 gene expression by reverse transcriptase-polymerase chain reaction and CpG hypermethylation of the YPEL3 promoter by base-specific polymerase chain reaction analysis. Colon cancer cell lines (Caco-2 and HCT116−/− p53) were used to assess YPEL3 gene expression after treatment with 5-azadeoxycytidine or trichostatin A. Results Reverse transcriptase-polymerase chain reaction analysis demonstrated a decrease in YPEL3expression in tumor samples when compared to their patient-matched normal tissue. We determined that DNA methylation of the YPEL3 promoter CpG island does not play a role in YPEL3 regulation in human colon tumors or colon cancer cells lines, consistent with the
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Due to its role in aging and antitumor defense, cellular senescence has recently attracted increasing interest. However, [the] detection of senescent cells remains difficult due to the lack of specific biomarkers. ndeed, most determinants of cellular senescence, such as the upregulation of p53, p16Ink4a, p21WAF/CIP1 or SASP-associated cytokines, are not exclusively observed in senescence, but can also occur in other types of stress responses. In addition, alterations like SAHF or DNA-SCARS formation are frequently observed, but not necessarily a mandatory feature or exclusive to senescent cells. The current gold standard for the detection of senescence is the so-called senescence-associated β-galactosidase (SA-β-Gal) activity. Although SA-β-Gal has been first suggested as a distinct enzyme, its activity is derived from lysosomal β-Gal encoded by the GLB1 gene. β-Gal is an accepted marker of senescence, but its reliability and specificity have been questioned, as a positive β-Gal reaction ...
p53 protein levels increase in HDFs, such as IMR90 and MRC5, during replicative senescence (8-11). Moreover, p53 sequence-specific DNA-binding activity and transcriptional activity also increase during replicative senescence (9, 12). These studies (8-12) have suggested a role for p53 in the onset and maintenance of cellular senescence. Consistent with this idea, the p53-mediated induction of p21 and Gadd45 genes in normal human cells is known (13, 16, 17) to play a role in cell growth arrest. However, the number of p53 target genes whose expression is induced during cellular senescence in HDFs remains rather limited. Therefore, our observations that p53 activates the transcription of IFI16, a candidate cellular senescence gene, in response to certain DNA damage signals in normal human fibroblasts are important.. The IFI16 protein is an IFN-inducible protein and treatment of a variety of cells with IFNs (α, β, or γ) has been shown to result in up-regulation of the IFI16 mRNA and protein (21). ...
Cellular senescence is a state of permanent cell cycle arrest in which a cell is unable to further divide in response to normal growth stimuli. Telomere shortening, believed to be a mechanism of cellular senescence, is a result of numerous rounds of cell division and can be accelerated by heightened levels of oxidative stress. An accumulation of senescent T lymphocytes in blood and tissues has been suggested to contribute to the general immunosuppression seen in the elderly. Obese individuals and athletes taking part in regular high intensity exercise are subjected to heightened states of oxidative stress which appears to result in immunosuppression and increased susceptibility to infection. It was hypothesised that there would be an accumulation of senescent T lymphocytes with ageing, with obesity and during six months training for an Iron man competition ...
How long can human beings live? Is there an outside limit? Do we know enough about aging to break through possible biological barriers? Is the current approach to curing "age associated diseases" like Alzheimers flawed? Experts are sharply divided.. In 1962 eminent biologist Leonard Hayflick discovered that normal human fetal cells replicate a limited number of times. This phenomenon promptly acquired the moniker the "Hayflick Limit." Later, biologists Calvin Harley and Carol Greider provided the molecular explanation for the Hayflick limit with their discovery that telomeres, the DNA biological material in every cell of our bodies, diminish each time cells divide.. In contrast, cancer cells, which are immortal, produce an enzyme called telomerase that maintains the length of telomeres and enables cancer cells to replicate without limit. The strategy of extending the life of normal cells by injecting telomerase has proven thorny, as reported by Dr. Elizabeth Blackburn, co-discoverer of ...
To determine whether 1,25-dihydroxyvitamin D (1,25(OH)2 D) can exert an anti-osteoporosis role through anti-aging mechanisms, we analyzed the bone phenotype of mice with 1,25(OH)2 D deficiency due to deletion of the enzyme, 25-hydroxyvitamin D 1α-hydroxylase, while on a rescue diet. 1,25(OH)2 D deficiency accelerated age-related bone loss by activating the p16/p19 senescence signaling pathway, inhibiting osteoblastic bone formation, and stimulating osteoclastic bone resorption, osteocyte senescence, and senescence-associated secretory phenotype (SASP). Supplementation of exogenous 1,25(OH)2 D3 corrected the osteoporotic phenotype caused by 1,25(OH)2 D deficiency or natural aging by inhibiting the p16/p19 pathway. The proliferation, osteogenic differentiation, and ectopic bone formation of bone marrow mesenchymal stem cells derived from mice with genetically induced deficiency of the vitamin D receptor (VDR) were significantly reduced by mechanisms including increased oxidative stress, DNA ...
Cellular senescence is a physiological phenomenon that has both beneficial and detrimental consequences. Senescence limits tumorigenesis and tissue damage throughout the lifetime. However, at the late stages of life, senescent cells increasingly accumulate in tissues and might also contribute to the development of various age-related pathologies. Recent studies have revealed the molecular pathways that preserve the viability of senescent cells and the ones regulating their immune surveillance. These studies provide essential initial insights for the development of novel therapeutic strategies for targeting senescent cells. At the same time they stress the need to understand the limitations of the existing strategies, their efficacy and safety, and the possible deleterious consequences of senescent cell elimination. Here we discuss the existing strategies for targeting senescent cells and upcoming challenges in translating these strategies into safe and efficient therapies. Successful translation ...
Cellular senescence is a normal consequence of aging, resulting from lifelong accumulation of DNA damage that triggers an end to cell replication. Although senescent cells no longer divide, they persist in their tissue of origin and develop characteristics that can hasten and exacerbate age-related disease. This series addresses the contribution of cellular senescence to cardiovascular, neurodegenerative, and arthritic disorders as well as the senescent phenotypes in various tissues and cell types. In addition to their cell-intrinsic effects, senescent cells develop the ability to negatively influence healthy neighboring cells and immune cells by secreting senescence-associated set of cytokines and mediators known as the SASP. These reviews also highlight ongoing efforts to accurately identify, target, and eliminate senescent cells or otherwise combat their deleterious effects in disease. One day, this work may provide the basis for therapies targeting aging cells in multiple organs.. ...
Tumor development is a multi-step process driven by the collective action of gain-of-function mutations in oncogenes and loss-of-function alterations in tumor suppressor genes. The particular spectrum of mutations in a given cancer is rarely the result of random chance but instead derives from the intimate connections between proliferative networks and those suppressing growth and transformation. Specifically, hyper-active oncogenes directly engage tumor suppressor programs, such that cells harboring oncogenic lesions frequently must acquire secondary mutations that disable these anti-proliferative responses before progressing to overt transformation. This tight coupling represents a critical checkpoint protecting against tumor formation. Whether different cell types exhibit variability in the extent and/or timing of this oncogene-induced tumor suppression is largely unknown. The ability of oncogenic Ras to induce the tumor suppressive p1 9 Arf-p5.3 pathway and cause irreversible cell cycle ...
Several previous studies have pointed to the functional significance of H4K20me3 in senescent and progeroid cells [33, 34]. Here we have confirmed that H4K20me3 is also upregulated in senescent cells in vivo, specifically OIS melanocytes. Compared with proliferating cells, H4K20me3 is relatively enriched in both RS and OIS cells in at least three features of the genome. First, based on immunofluorescence and ChIP-seq analysis, H4K20me3 is enriched in heterochromatic SAHF. Here, H4K20me3 co-localizes with another heterochromatic modification, H3K9me3. H3K9me3 is indirectly responsible for recruitment of SUV420H2 and H4K20me3 to chromatin [49, 55], and in SAHF, H4K20me3 specifically overlapped with H3K9me3, not late-replicating DNA. Thus, H3K9me3 is likely responsible for recruitment of H4K20me3 to SAHF. Previously, we showed that telomeres are largely excluded from SAHF in RS cells [70]. In line with this initially surprising observation and enrichment of H4K20me3 in SAHF, we show here that ...
BMI1 plays critical roles in maintaining the self-renewal of hematopoietic, neural, intestinal stem cells, and cancer stem cells (CSCs) for a variety of cancer types. BMI1 promotes cell proliferative life span and epithelial to mesenchymal transition (EMT). Upregulation of BMI1 occurs in multiple cancer types and is associated with poor prognosis. Mechanistically, BMI1 is a subunit of the Polycomb repressive complex 1 (PRC1), and binds the catalytic RING2/RING1b subunit to form a functional E3 ubiquitin ligase. Through mono-ubiquitination of histone H2A at lysine 119 (H2A-K119Ub), BMI1 represses multiple gene loci; among these, the INK4A/ARF locus has been most thoroughly investigated. The locus encodes the p16INK4A and p14/p19ARF tumor suppressors that function in the pRb and p53 pathways, respectively. Its repression contributes to BMI1-derived tumorigenesis. BMI1 also possesses other oncogenic functions, specifically its regulative role in DNA damage response (DDR). In this process, BMI1
The amount of cellular proteins is a crucial parameter that is known to vary between cells as a function of the replicative passages, and can be important during physiological aging. The process of protein degradation is known to be performed by a series of enzymatic reactions, ranging from an initial step of protein ubiquitination to their final fragmentation by the proteasome. In this paper we propose a stochastic dynamical model of nuclear proteins concentration resulting from a balance between a constant production of proteins and their degradation by a cooperative enzymatic reaction. The predictions of this model are compared with experimental data obtained by fluorescence measurements of the amount of nuclear proteins in murine tail fibroblast (MTF) undergoing cellular senescence. Our model provides a three-parameter stationary distribution that is in good agreement with the experimental data even during the transition to the senescent state, where the nuclear protein concentration changes
The above studies suggest that senescent cells may accumulate with age and at sites of pathology in the brain. However, the significance of senescent cells in both the induction and exacerbation of neurodegenerative disorders is unknown. To date, it has been extremely difficult to discern the overall significance and mechanistic contribution of senescent cells to neuropathology because of a lack of tools to identify, isolate, and/or eliminate these cells. Current methods rely on a combination of markers, including those described in Figure 1. As these markers are not truly unique to senescent cells, it is imperative to establish that these changes occur in the context of senescence and not just as a result of inflammation, for example. A true demonstration that senescent cells causally drive neuropathology can be achieved either by prevention of senescence entry through genetic inactivation of p16INK4A or by direct elimination of senescent cells using genetically engineered mice. To date, these ...
The accumulation of senescent cells is implicated in the pathology of several age-related diseases. While the clearance of senescent cells has been suggested as a therapeutic target for patients with osteoarthritis (OA), cellular senescence of bone-resident osteoblasts (OB) remains poorly explored. Since oxidative stress is a well-known inducer of cellular senescence, we here investigated the effect of antioxidant supplementation on the isolation efficiency, expansion, differentiation potential, and transcriptomic profile of OB from osteoarthritic subchondral bone. Bone chips were harvested from sclerotic and non-sclerotic regions of the subchondral bone of human OA joints. The application of 0.1 mM ascorbic acid-2-phosphate (AA) significantly increased the number of outgrowing cells and their proliferation capacity. This enhanced proliferative capacity showed a negative correlation with the amount of senescent cells and was accompanied by decreased expression of reactive oxygen species (ROS) in
Upon successful chemotherapy, cancer cells undergo either apoptosis or senescence. Whereas the mechanism of cancer cell apoptosis is relatively well understood, there is only scant knowledge on how chemotherapy-induced cancer senescence occurs. Here we report that a cascade of secreted proteins, plasminogen activator inhibitor 1 (PAI-1) - tissue-type plasminogen activator (t-PA) - insulin-like growth factor-binding protein 3 (IGFBP3), mediates chemotherapy-induced senescence of breast cancer cells.. MCF-7 breast cancer cells display robust senescence induction upon doxorubicin treatment and we found that the conditioned medium from senescent MCF-7 cells can induce senescence in non-senescent MCF-7 cells, which suggested the presence of secreted mediator(s) of senescence. To identify such mediator(s), we undertook a quantitative proteomic analysis of the protein secretion from senescent MCF-7 cells and observed significantly increased levels of secreted IGFBP3. Increased extracellular IGFBP3 ...
Supplement Senescence pertains to the biological aging of a living thing. It entails the gradual deterioration of morphological features and function of a cell or of the whole organism. On the cellular level, senescence is that stage in a diploid cells cycle wherein it ceases to divide. For instance, a typical fibroblast cell may undergo a maximum of 50 mitotic divisions and then becomes senescent. This is referred to as the Hayflick phenomenon.1 It naturally occurs and results from the shortening of telomeres that eventuates in DNA damage. Cellular senescence is also associated with excessive exposure to reactive oxygen species, oncogene activation, and cell to cell fusion. When a cell is in senescence, it no longer divides but still remains metabolically active. At the level of the whole organism, senescence is manifested when the organism ages, i.e. the ability to function and deal with stress deteriorates thereby increases its vulnerability to dysfunction and diseases. ...
2005). These secreted molecules affect nearby cells to provoke inflammatory responses, eventually producing aging-related chronic inflammation called inflammaging, one type of sterile persistent inflammation. Thus, long-term stimulation by SASP molecules induces various metabolic changes including cardiovascular changes (Franceschi and Campisi, 2014). Sometimes they lead to late-stage cancer (Campisi, 2013). Thus, blocking SASP production may be effective for achieving healthy aging. Many laboratories have been searching for agents to prevent the aging process itself. However, in our opinion, stopping cellular senescence may have other harmful effects on the body. Blocking cells to go into senescence cells means that they still have proliferating capacity, although they are old. This may deleteriously lead to cancer formation. In this respect, inhibition of SASP formation without affecting aging capacity (inhibition of inflammaging) seems to be a safe new target for healthy aging. To prove the ...
The human population is getting ageing. Both ageing and age-related diseases are correlated with an increased number of senescent cells in the organism. Senescent cells do not divide but are metabolically active and influence their environment by secreting many proteins due to a phenomenon known as senescence associated secretory phenotype (SASP). Senescent cells differ from young cells by several features. They possess more damaged DNA, more impaired mitochondria and an increased level of free radicals that cause the oxidation of macromolecules. However, not only biochemical and structural changes are related to senescence. Senescent cells have an altered chromatin structure, and in consequence, altered gene expression. With age, the level of heterochromatin decreases, and less condensed chromatin is more prone to DNA damage. On the one hand, some gene promoters are easily available for the transcriptional machinery; on the other hand, some genes are more protected (locally increased level of ...
Cellular senescence is the point at which our cells stop dividing and growing due to damage or lack of necessary components. As cells age, they lose their ability to actively divide and start to undergo senescence.
Human gene GC6 is expressed more abundantly in senescent cells than young cells. Isolated, purified, and recombinant nucleic acids and proteins corresponding to the human GC6 gene and its mRNA and protein products, as well as peptides and antibodies corresponding to the GC6 protein can be used to identify senescent cells, distinguish between senescent and young cells, identify agents that alter senescent gene expression generally and GC6 expression specifically; such agents as well as GC6 gene and gene products and products corresponding thereto can be used to prevent and treat diseases and conditions relating to cell senescence.
First Myc oncogene triggers apoptosis in the lymphoma cells. The dying cells attract macrophages of the immune system, which devour and dispose of the dead lymphoma cells. The thus activated macrophages secrete messenger molecules (cytokines), including the cytokine TGF-beta, which can block the growth of cancer cells in the early stage of a tumor disease, by switching on the senescence program ...
Senescent cells are metabolically active but no longer capable of dividing, contribute to aging. Senescence is a key mechanism for preventing the spread of cancer cells.
Senescence-inducing therapies can block proliferation of malignant cells and promote anti-tumor immune activity. However, the risk of tumor relapse remains high due to the long lifespan of senescence cells with potential to escape senescence. Here our preclinical studies demonstrate that combining a senescent-inducing aurora kinase A (AURKA) inhibitor alisertib (MLN8237) with an MDM2 antagonist [(-)-nutlin 3a] effectively induces robust p53 activation in senescent Tp53WT tumors accompanied by: 1) tumor cell proliferation arrest; 2) mitochondrial depolarization and tumor cell apoptosis; and 3) tumor cell clearance via CCL5-, CCL1- and CCL9-mediated recruitment of anti-tumor leukocytes. This combined therapy shows adequate bioavailability and low toxicity to the host in the mouse model. Moreover, the prominent preclinical response of patient-derived melanoma tumors to the co-targeting of MDM2 and AURKA provides rationale for further investigation of alisertib and MDM2 inhibitors.. Citation Format: ...
from Jules: this appears to me to be THE POSTER of CROI because its the first connection between a clinical comorbidity outcome & senescence. The findings were in a relatively more advanced patient population so a key question is if you look at patients with high CD4s of say 650 and treat them with HAART will you see similar correlation with senescence; my guess is yes, senescence occurs as a result of activation & inflammation which is ongoing at some level regardless of CD4 count & undetectable viral load due to the presence of virus, HIV, regardless of whether its low or high virus levels. Perhaps the degree of senescence is less if CD4 is high & viral load low but thisT is one of many studies that need to be conducted but I think yes you will still find senescence, maybe not as often or as much but it appears HIV causes senescence ...
Using models of replicative and stress-induced premature senescence (oxidative stress, hyperglycaemia) as well as endothelial cells prepared from young and aged mice, we will identify PTMs (glycosylation, acetylation, oxidation, AGE modification) of AMPK and its regulator proteins. We will study the effects of detected PTMs on AMPK phosphorylation and activation as well as on AMPK functions, such as regulation of autophagy, permeability, angiogenesis and glucose metabolism. Furthermore, we will investigate whether the observed PTMs are related to changes of the cellular redox state (e.g. increased generation of reactive oxygen species and/or decreased antioxidative capacity), to an altered histone acetyltransferase/histone deacetylase balance or to changes in glucose metabolisation through the hexosamine pathway. The reversibility or prevention of the identified PTMs will be tested by modifying the antioxidant defence (e.g. overexpression of thioredoxin), by modulating histone deacetylases such ...
Cellular senescence, a term originally defining the characteristics of cultured cells that exceed their replicative limit, has been broadened to describe durable states of proliferative arrest induced by disparate stress factors. Proposed relationships between cellular senescence, tumour suppression, loss of tissue regenerative capacity and ageing suffer from lack of uniform definition and consistently applied criteria. Here, we highlight caveats in interpreting the importance of suboptimal senescence-associated biomarkers, expressed either alone or in combination. We advocate that more-specific descriptors be substituted for the now broadly applied umbrella term senescence in defining the suite of diverse physiological responses to cellular stress.
The purpose of the cytokines is to repair tissue. In the SASP secretome, they are perhaps trying to summon the immune system, communicating to the rest of the tissue that there is a problem. The immune system does arrive and kill most senescent cells, but 10-15% survive, perhaps due to the over-expression of matrix metalloproteinases (MMPs) which can cleave the ligands off the cell surface where natural killer cells would bind, allowing the cell to escape the immune system ...
Genetic analysis of TP63 implicates ΔNp63 isoforms in preservation of replicative capacity and cellular lifespan within adult stem cells. ΔNp63α is also an oncogene and survival factor that mediates therapeutic resistance in squamous carcinomas. These diverse activities are the result of genetic and functional interactions between TP63 and an array of morphogenic and morphostatic signals that govern tissue and tumor stasis, mitotic polarity, and cell fate; however the cellular signals that account for specific functions of TP63 are incompletely understood. To address this we sought to identify signaling pathways that regulate expression, stability or activity of ΔNp63α. An siRNA-based screen of the human kinome identified the Type 1 TGFβ receptor, ALK5, as the kinase required for phosphorylation of ΔNp63α at Serine 66/68 (S66/68). This activity is TGFβ-dependent and sensitive to either ALK5-directed siRNA or the ALK5 kinase inhibitor A83-01. Mechanistic studies support a model in which ALK5 is
Cancer is a heterogeneous disease characterized by unregulated cell growth (1). Throughout oncogenesis, the development of a cancerous phenotype, tumor cells undergo several distinct events required for survival, such as immortalization and transformation (2). In this chapter, we will begin by focusing on the process of immortalization and its associated properties. Immortalization refers to the acquired ability of a cell to divide indefinitely in culture (2). The term was originally coined in 1912 by Alexis Carrel, a biologist and surgeon. He hypothesized that all mammalian cells, when extracted from living tissue and grown in a Petri dish, could grow indefinitely when provided with sufficient space and nutrients required for proliferation (2). However, in 1961, scientists Leonard Hayflick and Paul Moorhead made it well known that normal cells explanted (i.e., taken from living tissue) into culture have a limited replicative lifespan (2). Once a normal cell has reached its limited replicative ...
The promyelocytic leukemia gene (PML) critically regulates several cellular functions that oppose tumorigenesis such as oncogene-induced senescence, apoptosis, the response to DNA damage and to viral infections. PML deficiency occurs commonly in a broad spectrum of human cancers through mechanisms that involve its aberrant ubiquitination and degradation. Furthermore, several viruses encode viral proteins that promote viral replication through degradation of PML. These observations suggest that restoration of PML should lead to potent anti-tumor effects or antiviral responses. In this review we will summarize the mechanisms involved in PML degradation with the intent to highlight novel therapeutic strategies to trigger PML restoration.
Sigma-Aldrich offers abstracts and full-text articles by [M C Ramello, J Tosello Boari, F P Canale, H A Mena, S Negrotto, B Gastman, A Gruppi, E V Acosta Rodríguez, C L Montes].
p53 is produced as various isoforms as the result of alternative splicing and promoter usage. One isoform, p53-beta, accelerates cellular arrest, while another isoform, delta-133p53 represses replicative senescence in cultured cells. In this issue of the Journal of Clinical Investigation, Abdul Mondal and colleagues at the National Cancer Institute evaluated the expression of these two p53 isoforms in T lymphocytes from healthy donors and donors with lung cancer.
The p15 tumor suppressor (CDKN2B) is located in the same region as p16 (CDKN2A), and is also involved in cell cycle, senescence and cancer. This region is frequently mutated and/or deleted in a wide variety of tumors [2229]. Genetic variants have been identified close to both p15 and p16 in patients with type 2 diabetes and cardiovascular disease [2230]. Although CDKN2B seems to have a role in cellular senescence and age-related diseases, its implication in broader aspects of ageing is still unknown. ...
Gambino V, De Michele G, Venezia O, Migliaccio P, DallOlio V, Bernard L, Minardi SP, Della Fazia MA, Bartoli D, Servillo G, Alcalay M, Luzi L, Giorgio M, Scrable H, Pelicci PG, Migliaccio E. Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging. Aging Cell. 2013 Jun; 12(3):435-45. Epub 2013 Mar 27 ...
iPS Efficiency Check qPCR Kit - assess your target cells reprogrammability. Measure senescence marker levels and test to verify iPS generation.
iPS Efficiency Check qPCR Kit - assess your target cells reprogrammability. Measure senescence marker levels and test to verify iPS generation.
The new research work on senolyic drugs by Baar et al. uses a rationally designed molecule that selectively targets senescent cells in vivo, both in an
Part of the Hallmarks of Aging series. Did you know you have two different ages? The obvious one is chronological age, or the number of years since yo.... ...
Eros Di Giorgio, Harikrishnareddy Paluvai, Emiliano Dalla, Liliana Ranzino, Alessandra Renzini, Viviana Moresi, Valentina Cutano, Raffaella Picco, Claudio Brancolini
A Theory that explains the evolution of senescence that focuses on the effects of redundancy in the genetic architecture on Mate-Selection, and on the negative effects of scale, on fitness . Together these effects drive the senescence of the individual conserving resources for progeny.
Although the induction of senescence in cancer cells is a potent mechanism of tumor suppression, senescent cells remain metabolically active and may secrete a broad spectrum of factors that promote tumorigenicity in neighboring malignant cells. Here we show that androgen deprivation therapy (ADT), a widely used treatment for advanced prostate cancer, induces a senescence-associated secretory phenotype in prostate cancer epithelial cells, indicated by increases in senescence-associated beta-galactosidase activity, heterochromatin protein 1 beta foci, and expression of cathepsin B and insulin-like growth factor binding protein 3. Interestingly, ADT also induced high levels of vimentin expression in prostate cancer cell lines in vitro and in human prostate tumors in vivo. The induction of the senescence-associated secretory phenotype by androgen depletion was mediated, at least in part, by down-regulation of S-phase kinase-associated protein 2, whereas the neuroendocrine differentiation of prostate ...
Premature senescence of human diploid fibroblasts (HDFs) can be induced by exposures to a variety of oxidative stress and DNA damaging agents. In this study we developed a robust model of UVB-induced premature senescence of skin HDFs. After a series of 10 subcytotoxic (non-proapoptotic) exposures to UVB at 250 mJ/cm2, the so-called biomarkers of senescence were markedly expressed: growth arrest, senescence-associated β-galactosidase activity, senescence-associated gene overexpression, deletion in mitochondrial DNA. A set of 44 stress- and senescence-associated genes were found to be differentially expressed in this model, among which clusterin/apolipoprotein J (apo J) and transforming growth factor-β1 (TGF-β1). Transfection of apo J cDNA provided protection against premature senescence-inducing doses of UVB and other stressful agents. Neutralizing antibodies against TGF-β1 or its receptor II (TβRII) sharply attenuated the senescence-associated features, suggesting a role for TGF-β1 in ...
TY - JOUR. T1 - Suppression of Nucleotide Metabolism Underlies the Establishment and Maintenance of Oncogene-Induced Senescence. AU - Aird, Katherine M.. AU - Zhang, Gao. AU - Li, Hua. AU - Tu, Zhigang. AU - Bitler, Benjamin G.. AU - Garipov, Azat. AU - Wu, Hong. AU - Wei, Zhi. AU - Wagner, Stephan N.. AU - Herlyn, Meenhard. AU - Zhang, Rugang. PY - 2013/4/25. Y1 - 2013/4/25. N2 - Oncogene-induced senescence is characterized by a stable cell growth arrest, thus providing a tumor suppression mechanism. However, the underlying mechanisms for this phenomenon remain unknown. Here, we show that a decrease in deoxyribonucleotide triphosphate (dNTP) levels underlies oncogene-induced stable senescence-associated cell growth arrest. The decrease in dNTP levels is caused by oncogene-induced repression of ribonucleotide reductase subunit M2 (RRM2), a rate-limiting protein in dNTP synthesis. This precedes the senescence-associated cell-cycle exit and coincides with the DNA damage response. Consistently, ...
Curcuminoids are well known for their capabilities to combat risk factors that are associated with ageing and cellular senescence. Recent reports have demonstrated that curcuminoids can extend the lifespan of model organisms. However, the underlying mechanisms by which these polyphenic compounds exert these beneficial effects remain unknown. In this study, t-BHP-induced premature senescence model in human fibroblasts was chosen to explore the protective effects of a curcuminoid, bisdemethoxycurcumin (BDMC), on cellular senescence. The results demonstrated that BDMC attenuated oxidative stress-induced senescence-like features which include the induction of an enlarged cellular appearance, higher frequency of senescence-associated beta-galactosidase staining activity, appearance of senescence-associated heterochromatic foci in nuclei, decrease in proliferation capability, and alteration inrelated molecules such as p16 and retinoblastoma protein. Notably, we found that BDMC treatment activated ...
The Wnt signaling pathway has key roles in development and generally promotes proliferation of stem cells and inhibits apoptosis. These effects are essentially opposite to the changes that occur in senescent stem cells. Thus, Ye et al. examined whether reduced Wnt signaling might have a role inhibitory in senescence. They monitored the formation of specialized domains of heterochromatin known as senescence-associated heterochromatin foci or SAHF, which are thought to repress transcription of genes that promote proliferation. In human WI38 fibroblasts, expression of Wnt2 mRNA was decreased as cells approached senescence. Formation of SAHF was inhibited when pharmacological inhibitors were used to decrease activity of glycogen synthase kinase 3β (a kinase activated downstream of Wnt). Furthermore, small hybrid RNAs were used to decrease expression of Wnt2 in young fibroblasts, and this promoted formation of SAHF, the authors marker of senescence. Accordingly, exposure of cells to a Wnt ligand ...
Cellular senescence (deterioration) is a critical factor of biological aging that occurs in almost all peripheral tissues but little is known about its role in age-related neurodegenerative disorders, such as Parkinsons disease (PD). Senescence occurs in dividing cell types and halts cell proliferation (growth) in an irreversible manner. This process is caused by stress and puts cells at risk for tumor formation. Once established, these cells express a senescence-associated secretory phenotype (SASP), the pro-inflammatory secretion of cytokines and other factors that contribute to the age-related loss of peripheral tissue function. We aim to interrogate induction of senescence and SASP in response to alpha-synuclein (protein clumps) within the most prevalent dividing cell type in the brain, the astrocyte (cells that provide support and clean waste in the brain), and how this in turn affects dopaminergic cell health in relation to PD.. Hypothesis ...
OBJECTIVE: Human diploid fibroblasts undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular aging. The beneficial effects of vitamin E in aging have been established, but studies to determine the mechanisms of these effects are ongoing. This study determined the molecular mechanism of γ-tocotrienol, a vitamin E homolog, in the prevention of cellular aging in human diploid fibroblasts using the expression of senescence-associated genes. METHODS: Primary cultures of young, pre-senescent, and senescent fibroblast cells were incubated with γ-tocotrienol for 24 h. The expression levels of ELN, COL1A1, MMP1, CCND1, RB1, and IL6 genes were determined using the quantitative real-time polymerase chain reaction. Cell cycle profiles were determined using a FACSCalibur Flow Cytometer. RESULTS: The cell cycle was arrested in the G0/G1 phase, and the percentage of cells in S phase decreased with senescence. CCND1, ...
Sigma-Aldrich offers abstracts and full-text articles by [Suzana Makpol, Azalina Zainuddin, Kien Hui Chua, Yasmin Anum Mohd Yusof, Wan Zurinah Wan Ngah].
Link to Pubmed [PMID] - 27503890. Proc. Natl. Acad. Sci. U.S.A. 2016 Aug;113(34):E5024-33. Oncogene-induced senescence (OIS) is a critical tumor-suppressing mechanism that restrains cancer progression at premalignant stages, in part by causing telomere dysfunction. Currently it is unknown whether this proliferative arrest presents a stable and therefore irreversible barrier to cancer progression. Here we demonstrate that cells frequently escape OIS induced by oncogenic H-Ras and B-Raf, after a prolonged period in the senescence arrested state. Cells that had escaped senescence displayed high oncogene expression levels, retained functional DNA damage responses, and acquired chromatin changes that promoted c-Myc-dependent expression of the human telomerase reverse transcriptase gene (hTERT). Telomerase was able to resolve existing telomeric DNA damage response foci and suppressed formation of new ones that were generated as a consequence of DNA replication stress and oncogenic signals. Inhibition ...
Glycans play essential roles in biological functions such as differentiation and cancer. Recently, glycans have been considered as biomarkers for physiological aging. However, details regarding the specific glycans involved are limited. Here, we investigated cellular senescence- and human aging-dependent glycan changes in human diploid fibroblasts derived from differently aged skin donors using a lectin microarray. We found that α2-6sialylated glycans in particular differed between elderly- and fetus-derived cells at early passage. However, both cell types exhibited sequentially decreasing α2-3sialylated O-glycan structures during the cellular senescence process and showed similar overall glycan profiles. We observed a senescence-associated decrease in sialylation and increase in galactose exposure. Therefore, glycan profiling using lectin microarrays might be useful for the characterization of biomarkers of aging.
Senescent fibroblasts are known to promote tumor growth. However, the exact mechanism remains largely unknown. An important clue comes from recent studies linking autophagy with the onset of senescence. Thus, autophagy and senescence may be part of the same physiological process, known as the autophagy-senescence transition (AST). To test this hypothesis, human fibroblasts immortalized with telomerase (hTERT-BJ1) were stably transfected with autophagy genes (BNIP3, CTSB or ATG16L1). Their overexpression was sufficient to induce a constitutive autophagic phenotype, with features of mitophagy, mitochondrial dysfunction and a shift toward aerobic glycolysis, resulting in L-lactate and ketone body production. Autophagic fibroblasts also showed features of senescence, with increased p21(WAF1/CIP1), a CDK inhibitor, cellular hypertrophy and increased β-galactosidase activity. Thus, we genetically validated the existence of the autophagy-senescence transition. Importantly, autophagic-senescent ...
The ends of linear chromosomes in eukaryotic cells are protected by telomeres. The telomeric DNA interacts with many proteins including the telomerase enzyme complex that extends telomere ends and compensates for the end replication problem. Human stem and cancer cells express telomerase to facilitate immortality. Without telomerase however, telomeres shorten with each round of DNA replication; this gradual erosion eventually leads to cell senescence, an irreversible cell cycle arrest, and serves to control cellular life span.
TY - JOUR. T1 - A genome-wide loss-of-function screen identifies SLC26A2 as a novel mediator of TRAIL resistance. AU - Dimberg, Lina Y.. AU - Towers, Christina G.. AU - Behbakht, Kian. AU - Hotz, Taylor J.. AU - Kim, Jihye. AU - Fosmire, Susan. AU - Porter, Christopher C.. AU - Tan, Aik-Choon. AU - Thorburn, Andrew. AU - Ford, Heide L.. PY - 2017/4/1. Y1 - 2017/4/1. N2 - TRAIL is a potent death-inducing ligand that mediates apoptosis through the extrinsic pathway and serves as an important endogenous tumor suppressor mechanism. Because tumor cells are often killed by TRAIL and normal cells are not, drugs that activate the TRAIL pathway have been thought to have potential clinical value. However, to date, most TRAIL-related clinical trials have largely failed due to the tumor cells having intrinsic or acquired resistance to TRAIL-induced apoptosis. Previous studies to identify resistance mechanisms have focused on targeted analysis of the canonical apoptosis pathway and other known regulators of ...
Cardiomyocytes cease to divide shortly after birth and an irreversible cell cycle arrest is evident accompanied by the downregulation of cyclin-dependent kinase activities. To get a better understanding of the cardiac cell cycle and its regulation, the effect of functional recovery of the mitosis-promoting factor (MPF) consisting of cyclin B1 and the cyclin-dependent kinase Cdc2 was assessed in primary cultures of postmitotic ventricular adult rat cardiomyocytes ( ARC). Gene transfer into ARC was achieved using the adenovirus-enhanced transferrinfection system that was characterized by the absence of cytotoxic events. Simultaneous ectopic expression of wild-type versions of cyclin B1 and Cdc2 was sufficient to induce MPF activity. Reestablished MPF resulted in a mitotic phenotype, marked by an abnormal condensation of the nuclei, histone H3 phosphorylation and variable degree of decay of the contractile apparatus. Although a complete cell division was not observed, the results provided ...
TY - JOUR. T1 - Epithelial innate immunity mediates tubular cell senescence after kidney injury. AU - Jin, Heng. AU - Zhang, Yan. AU - Ding, Qiong. AU - Wang, Shan Shan. AU - Rastogi, Prerna. AU - Dai, Dao Fu. AU - Lu, Dongmei. AU - Purvis, Madison. AU - Cao, Chao. AU - Wang, Angela. AU - Liu, Dingxiao. AU - Ren, Chongyu. AU - Elhadi, Sarah. AU - Hu, Ming Chang. AU - Chai, Yanfen. AU - Zepeda-Orozco, Diana. AU - Campisi, Judith. AU - Attanasio, Massimo. PY - 2019/1/24. Y1 - 2019/1/24. N2 - Acute kidney injury (AKI) is a common clinical condition of growing incidence. Patients who suffer severe AKI have a higher risk of developing interstitial fibrosis, chronic kidney disease, and end-stage renal disease later in life. Cellular senescence is a persistent cell cycle arrest and altered gene expression pattern evoked by multiple stressors. The number of senescent cells increases with age and even in small numbers these cells can induce chronic inflammation and fibrosis; indeed, in multiple organs ...
Project Description. Tumours are commonly described as wounds that do not heal. Tumours and chronic wounds comprise dysregulated epithelial cells, senescent fibroblasts, and share similar gene expression profiles. Fibroblast senescence is the major hallmark of chronic wounds, as proliferation defects prevent wound contraction and alters secretion that in turn directs epithelial cell behaviour. Cancer-associated fibroblasts (CAFs) play a similar role in tumour formation. Senescent CAFs promote the growth and metastasis of cancer cells.. Over time, fibroblasts naturally tend towards senescence, which results in a decrease in healing rates and predisposition towards cancer as we age. We recently discovered that low-intensity ultrasound can promote healing in mice with pathological healing defects caused by diabetes or old age, by reversing and protecting fibroblasts from senescence. This PhD will investigate the effect of ultrasound on CAF senescence, leading to the development of new cancer ...
posted from: A fair few good scientific papers on the role of cellular senescence in the progression of osteoarthritis have emerged in the last year. Given that UNITY Biotechnology aims to initially trial senolytic therapies to clear senescent cells as a treatment for inflammatory joint diseases, a list in which osteoarthritis features prominently, and that the UNITY principals now have quite a lot of funding to work with, I expect that well be hearing a lot more on this topic over the course of the next few years. There is nothing quite like the existence of a funded company in a field to spur a great deal more investment in related research from all sources. The rate at which reviews of the relevant science are published tends to increase as well, with the paper linked below as an example of the type.. Senescent cells accumulate in tissues with age, and that accumulation is thought to ...
09.30 - 09.45h Welcome/ Introduction: Clemens A. Schmitt Session I: 09.45 - 11.00h Chair: Fabrizio dAdda di Fagagna 09.45 - 10.15h Leonard Hayflick: A Brief History of the Discovery of the Relationship between Cell Senescence and Cancer 10.15 - 10.45h Jerry Shay: How Human Cells Bypass Telomere-associated Replicative Senescence In Cancer Development 10.45 - 11.00h Lars-Gunnar Larsson: Cdk2 inhibition delays Myc driven leukemia in vivo through restoration of cellular senescence (Abstract Talk) 11.00 - 11.30h Coffee break Session II: 11.30 - 12.45h Chair: Scott Lowe 11.30 - 12.00h Gerardo Ferbeyre: Regulation of E2F gene expression and senescence by the tumor suppressor PML 12.00 - 12.30h Masashi Narita: Gene expression in cellular senescence - from chromatin to proteins 12.30 - 12.45h Kristina Kirschner: Global analysis of tumour suppressor protein p53 shows plasticity in phenotype regulation (Abstract Talk) 12.45 - 14.15h Lunch/ Postersession Session III: 14.15 - 16.00h Chair: Daniel Peeper ...
Fibrosis involves activation of fibroblasts, increased production of collagen and fibronectin and transdifferentiation into contractile myofibroblasts. The process resembles aspects of wound-healing but remains unresolved and can be life-threatening when manifest in the kidneys, lungs and liver, in particular. The causes are largely unknown, but recent suggestions that repetitive micro-injury results in the eventual failure of epithelial cell repair due to replicative senescence are gaining favour. This is consistent with the onset of fibrotic diseases in middle age. Because epithelial injury often involves blood loss, inflammatory responses associated with the fibrotic response have been considered as therapeutic targets. However, this has proved largely unsuccessful and focus is now switching to earlier events in the process. These include EMT (epithelial-mesenchymal transition) and fibroblast activation in the absence of inflammation. TGFβ1 (transforming growth factor-β1) induces both EMT ...
Fibrosis involves activation of fibroblasts, increased production of collagen and fibronectin and transdifferentiation into contractile myofibroblasts. The process resembles aspects of wound-healing but remains unresolved and can be life-threatening when manifest in the kidneys, lungs and liver, in particular. The causes are largely unknown, but recent suggestions that repetitive micro-injury results in the eventual failure of epithelial cell repair due to replicative senescence are gaining favour. This is consistent with the onset of fibrotic diseases in middle age. Because epithelial injury often involves blood loss, inflammatory responses associated with the fibrotic response have been considered as therapeutic targets. However, this has proved largely unsuccessful and focus is now switching to earlier events in the process. These include EMT (epithelial-mesenchymal transition) and fibroblast activation in the absence of inflammation. TGFβ1 (transforming growth factor-β1) induces both EMT ...
d-galactose (d-gal)-induced cardiac alterations and Doxorubicin (Dox)-induced cardiomyocyte senescence are commonly used models to study cardiac aging. Accumulating evidence has suggested that microRNAs (miRNAs, miRs) are critically involved in the regulation of cellular and organismal aging and age-related diseases. However, little has been revealed about the roles of miRNAs in cardiac alterations induced by d-gal and Dox. In this study, we used miRNA arrays to investigate the dysregulated miRNAs in heart samples from 15month-old versus 2month-old male C57BL/6 mice and further validated them in d-gal-induced pseudo-aging mouse model and Dox-induced cardiomyocyte senescence in vitro model ...
Immune aging may underlie various aging-related disorders, including diminished resistance to infection, chronic inflammatory disorders, and autoimmunity. PD-1+ and CD153+ CD44high CD4+ T cells with features of cellular senescence, termed senescence-associated T (SA-T) cells, increasingly accumulate with age and may play a role in the immune aging phenotype. In this article, we demonstrate that, compared with young mice, the aged mouse environment is highly permissive for spontaneous proliferation of transferred naive CD4+ T cells, and it drives their transition to PD-1+ and CD153+ CD44high CD4+ T cells after extensive cell divisions. CD4+ T cells with essentially the same features as SA-T cells in aged mice are also generated from naive CD4+ T cells after extensive cell divisions under severe T-lymphopenic conditions by gamma irradiation or in developmental T cell defect, often in association with spontaneous germinal centers, as seen in aged mice. The increase in SA-T cells is significantly enhanced
This page contains the abstract: Premature T Cell Senescence in Ovx Mice Is Inhibited By Repletion of Estrogen and Medicarpin: A Possible Mechanism For Alleviating Bone Loss
"The aged microenvironment contributes to the age-related functional defects of CD4 T cells in mice". Aging Cell. 11 (5): 732-40 ... cells and the antigen-presenting function of dendritic cells is known to diminish with old age. The age-associated impairment ... Together with the age-related thymic involution, and the consequent age-related decrease of thymic output of new T cells, this ... The functional capacity of T-cells is most influenced by the effects of aging. In fact, age-related alterations are evident in ...
... cell death and aging". Aging. 3 (9): 821-8. doi:10.18632/aging.100380. PMC 3227447. PMID 21931183.. ... "Aging Cell. 9 (2): 236-42. doi:10.1111/j.1474-9726.2010.00553.x. PMC 3569090. PMID 20096034.. ... "Cell Stem Cell. 10 (5): 515-9. doi:10.1016/j.stem.2012.04.002. PMC 3561899. PMID 22560075.. ... "Can We Prevent Aging?". National Institute on Aging, US National Institutes of Health, Bethesda, MD. 29 July 2016. Archived ...
"Human longevity and common variations in the LMNA gene: a meta-analysis". Aging Cell. 11: 475-481. doi:10.1111/j.1474-9726.2012 ... Aging. 5: 653-61. doi:10.18632/aging.100594. PMC 3808698 . PMID 24244950. "ASA Fellows list". American Statistical Association ... A controversial paper regarding the genetics of aging with which she was associated was retracted from the journal Science in ... "The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts". AGE. 36: 933-943. doi: ...
Aging Cell. 16 (1): 52-60. doi:10.1111/acel.12525. PMC 5242303 . PMID 27618784. Kovacevic Z, Richardson DR (2007). "The ... 2002). "Enhanced expression of a novel protein in human cancer cells: a potential aid to cancer diagnosis". Cell Biol. Toxicol ... These authors strongly suggest a link between the increase in the MGMT DNA repair pathway and a delay in the aging process in ... Cell Biol. 118 (5): 399-408. doi:10.1007/s00418-002-0460-9. PMID 12432451. Strausberg RL, Feingold EA, Grouse LH, et al. (2003 ...
Mocchegiani, E; M. Malavolta (2004). «NK and NKT cell functions in immunosenescence». Aging Cell. 3 (4): 177-184. PMID 15268751 ... 2004). «Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells». Nature. 431 (7011): ... 2001). «Decreased natural killer cell activity is associated with atherosclerosis in elderly humans». Exp Gerontol. 37 (1): 127 ... Uyemura, K.; S. C. Castle, and T. Makinodan (2002). «The frail elderly: role of dendritic cells in the susceptibility of ...
Cell". 144 (1), s. 132-42, 01 2011. DOI: 10.1016/j.cell.2010.11.054. PMID: 21215375. PMCID: PMC3066439. (primary source) ... Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain. „Neurobiol Aging". ... Bartzokis G. Alzheimer's disease as homeostatic responses to age-related myelin breakdown. „Neurobiol. Aging". 32 (8), s. 1341- ... dostęp 2014-08-19]. Cytat: While scientists know Alzheimer's disease involves progressive brain cell failure, the reason cells ...
... when excess H2O2 accumulates in the cell, catalase converts it to H2O through this reaction: H. 2. O. 2. →. CAT. 1. 2. O. 2. + ... Weindruch, Richard (January 1996). "Calorie Restriction and Aging". Scientific American: 49-52.. ... Cells called phagocytes engulf pathogens and then use hydrogen peroxide to destroy them. The peroxide is toxic to both the cell ... Cell. 26 (1): 1-14. doi:10.1016/j.molcel.2007.03.016. PMID 17434122.. CS1 maint: Multiple names: authors list (link) ...
Lei M, Chuong CM (2016). "STEM CELLS. Aging, alopecia, and stem cells". Science. 351 (6273): 559-60. Bibcode:2016Sci...351.. ... Hair follicle aging. A key aspect of hair loss with age is the aging of the hair follicle.[45] Ordinarily, hair follicle ... "Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis". Science. 351 (6273): ... Aging of the hair follicle appears to be primed by a sustained cellular response to the DNA damage that accumulates in renewing ...
Weekes, Peter (16 September 2007). "Stem cell pioneer joins science exodus". The Age. Retrieved 3 September 2016. Fleming, ... when in fact the cells were germ cells from a fetal rat. In 2003 he was appointed a Personal Chair as Professor of Stem Cell ... "Cloning and Stem Cells". Archived from the original on 28 September 2007. "ISSCR Officers". International Society for Stem Cell ... a former Professor of Stem Cell Sciences and the Director of the Monash Immunology and Stem Cell Laboratories at Monash ...
"Development of the aging cell surface. Reduction of gap junction-mediated metabolic cooperation with progressive subcultivation ... "eat-5 and unc-7 represent a multigene family in Caenorhabditis elegans involved in cell-cell coupling". J. Cell Biol. 134 (2): ... "Connexin43 modulates cell polarity and directional cell migration by regulating microtubule dynamics". PLoS ONE. 6 (10): e26379 ... When cells are compromised due to disease or injury and start to die messages are transmitted to neighboring cells connected to ...
"Regenerative potential of human skeletal muscle during aging". Aging Cell. 1 (2): 132-9. doi:10.1046/j.1474-9728.2002.00017.x. ... but also in epidermal cells, in activated T cell and B cell lymphocytes, as well as in certain adult stem cells, but in the ... Epithelial stem cell tissue and its early daughter cells are the only noncancerous cells in which hTERT can be detected. Since ... A good example of immortal cancer cells is HeLa cells, which have been used in laboratories as a model cell line since 1951. ...
"Association between serum leptin concentration and white blood cell count in middle-aged Japanese men and women". Diabetes ... mammary epithelial cells, bone marrow,gastric chief cells and P/D1 cells. Leptin circulates in blood in free form and bound to ... as evidenced by its multiple sites of synthesis other than fat cells, and the multiple cell types beside hypothalamic cells ... Location of action Leptin acts directly on leptin receptors in the cell membrane of different types of cells in the human body ...
doi:10.1016/j.cell.2005.08.029. PMID 16169070. Fujihara J, Kunito T, Takeshita H (2007). "Frequency of two human glutathione-S- ... Aging. 26 (8): 1161-5. doi:10.1016/j.neurobiolaging.2004.11.001. PMID 15917099. Stelzl U, Worm U, Lalowski M, et al. (2005). "A ... 2005). "Three SNPs in the GSTO1, GSTO2 and PRSS11 genes on chromosome 10 are not associated with age-at-onset of Alzheimer's ... 2004). "Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease". Hum. Mol. Genet. ...
Aging. 33 (5): 1008.e17-23. doi:10.1016/j.neurobiolaging.2011.10.009. PMC 3306507 . PMID 22153900. Rusanescu G, Mao J (2014). " ... In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway ... "Notch3 is necessary for neuronal differentiation and maturation in the adult spinal cord". J. Cell. Mol. Med. 18 (10): 2103-16 ...
"Genomic instability and aging-like phenotype in the absence of mammalian SIRT6". Cell. 124 (2): 315-29. doi:10.1016/j.cell. ... "How Cells Age: Parallels between mice and yeast uncover a potentially universal aging mechanism". Technology Review. ... Adding resveratrol to the diet of mice inhibit gene expression profiles associated with muscle aging and age-related cardiac ... Cell. 135 (5): 907-18. doi:10.1016/j.cell.2008.10.025. PMC 2853975 . PMID 19041753. Barger JL, Kayo T, Vann JM, Arias EB, Wang ...
"Genomic instability and aging-like phenotype in the absence of mammalian SIRT6". Cell. 124 (2): 315-29. doi:10.1016/j.cell. ... "SIRT6 overexpression induces massive apoptosis in cancer cells but not in normal cells". Cell Cycle. 10 (18): 3153-58. doi: ... However, over-expression of SIRT6 in "middle-aged" and pre-senescent cells strongly stimulates HRR. This effect depends on the ... "SIRT6 rescues the age related decline in base excision repair in a PARP1-dependent manner". Cell Cycle. 14 (2): 269-76. doi: ...
Cell. 17 (3): 1228-38. doi:10.1091/mbc.E05-09-0899. PMC 1382312 . PMID 16407403. Shi H, Rojas R, Bonifacino JS, Hurley JH (2006 ... Aging. 28 (6): 883-4. doi:10.1016/j.neurobiolaging.2006.05.009. PMID 16784798. Rojas R, Kametaka S, Haft CR, Bonifacino JS ( ... Cell. 12 (10): 3242-56. doi:10.1091/mbc.12.10.3242. PMC 60170 . PMID 11598206. Strausberg RL, Feingold EA, Grouse LH, et al. ( ... Cell Biol. 6 (8): 763-9. doi:10.1038/ncb1153. PMID 15247922. Mingot JM, Bohnsack MT, Jäkle U, Görlich D (2005). "Exportin 7 ...
Aging. 23 (3): 389-396. doi:10.1016/S0197-4580(01)00335-9. PMID 11959401. Berggard T, Szczepankiewicz O, Thulin E, Linse S ( ... Cells. 13 (1): 21-7. PMID 11911470. Atack JR, Schapiro MB (2002). "Inositol monophosphatase activity in normal, Down syndrome ... L-690,488, a prodrug or L-690,330, has also been developed which has greater cell permeability. Treatment of cortical slices ... "The mood stabiliser lithium suppresses PIP3 signalling in Dictyostelium and human cells". Dis Model Mech. 2 (5-6): 306-12. doi: ...
Lee JH, Budanov AV, Karin M (Dec 2013). "Sestrins orchestrate cellular metabolism to attenuate aging". Cell Metab. 18 (6): 792- ... "Sestrins at the crossroad between stress and aging". Aging. 2 (6): 369-74. doi:10.18632/aging.100157. PMC 2919257 . PMID ... The encoded protein may function in the regulation of cell growth and survival. This protein may be involved in cellular ... "Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability". Oncogene. 21 (39): 6017-31. ...
"Transcriptional profiling of Alzheimer blood mononuclear cells by microarray". Neurobiol. Aging. 28 (12): 1795-809. doi:10.1016 ... Human C21orf59 genome location and C21orf59 gene details page in the ... Male Alzheimer's patients have shown a decrease in expression of C21orf59 in their blood cells. The C21orf59 gene lies within ... 2006). "Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins ...
"Human longevity and common variations in the LMNA gene: a meta-analysis". Aging Cell. 11: 475-481. doi:10.1111/j.1474-9726.2012 ... "anti-aging" and "age-management". He is author of the website and he has testified before the U.S. Congress, as ... for anti-aging and bodybuilding. A controversial paper regarding the genetics of aging with which Perls was associated was ... "Anti-Aging Quackery: Human Growth Hormone and Tricks of the Trade-More Dangerous Than Ever". Oxford Press. 2004. Retrieved 18 ...
2019-07-20: Cell Proliferation (journal). *2019-07-20: European Review of Aging and Physical Activity ...
Aging Cell. 10 (2): 198-207. doi:10.1111/j.1474-9726.2010.00657.x. PMID 21108730. Ferrari, Carlos K. B. (2004). "Functional ... The bottleneck exploits stochastic processes in the cell to increase in the cell-to-cell variability in mutant load as an ... The resulting reduction in per-cell copy number of mtDNA plays a role in the mitochondrial bottleneck, exploiting cell-to-cell ... the cells of the inner cell mass restrict mtDNA replication until they receive the signals to differentiate to specific cell ...
... in peripheral blood T-cells is a biomarker of human aging". Aging Cell. 8 (4): 439-48. doi:10.1111/j.1474-9726.2009.00489.x. ... Increased expression of the p16 gene as organisms age reduces the proliferation of stem cells. This reduction in the division ... p16 plays an important role in cell cycle regulation by decelerating cells progression from G1 phase to S phase, and therefore ... or senescence leads to the buildup of p16 in tissues and is implicated in aging of cells. Regulation of p16 is complex and ...
1995). "Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae". Cell. 80 (3): 485-96. doi:10.1016/0092-8674(95) ... 2007). "SIRT1 transgenic mice show phenotypes resembling calorie restriction". Aging Cell. 6 (6): 759-67. doi:10.1111/j.1474- ... Guarente's lab has studied the function of genes involved in aging. In 1993, Cynthia Kenyon's lab at UCSF discovered that a ... When SIRT4 was mutated in a single cell organism S. cerevisiae longevity was extended. It was later determined that the complex ...
T Cells to protect tumour cells. Nature Communications. March 2018, 9 (1): 948. PMC 5838096. PMID 29507342. doi:10.1038/s41467- ... The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annual Review of ... 细胞毒性T细胞(CTLs, killer T cells)负责杀伤被病毒感染的细胞和癌细胞,在对器官移植的免疫排斥中也有参与。其特点在于细胞表面的CD8蛋白质。它通过识别所有有核细胞表
Part of Vittorio Sebastianos job is to babysit a few million stem cells. The research professor of reproductive biology at ... Are germ cells immune to aging?. Yes and no. They definitely do age, but not to the same extent as other cell types. In males, ... Female cells do age, and the consensus is that there are no germ stem cells in the ovary so these cells lack a molecular ... which means it can become any other cell of the body-and you also revert the age of that cell to the youngest age possible. ...
"Stem Cells and Aging: A Chicken-Or-Egg Issue?". Aging and Disease. 3 (3): 260-268. Liang Y, Zant GV (2008). "Aging stem cells, ... The stem cell theory of aging is also a sub-category of cellular theories. Smith J., A., Daniel R. "Stem Cells and Aging: A ... The stem cell theory of aging postulates that the aging process is the result of the inability of various types of stem cells ... have reviewed evidence that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell ...
CELL DEATH Cell death during aging is an important issue, and it is important to understand what cell death is, and what it is ... Source for information on Cellular Aging: Cell Death: Encyclopedia of Aging dictionary. ... Encyclopedia of Aging COPYRIGHT 2002 The Gale Group Inc.. CELLULAR AGING: CELL DEATH. Cell death during aging is an important ... Cell death and aging. "Running out of cells" because of apoptosis does not cause aging. Nevertheless, apoptosis is considered ...
... and using key supplements may help your cells produce more energy and protect you against many diseases of aging. ... New Anti-Aging Drugs Focusing on Toxic Cells. Senescent cells can cause a number of age-related diseases, yet also perform ... Why Scientists Think Hacking Our Cells Could Turn Off the Aging Process. Written by Marsha McCulloch, MS, RD. on February 27 ... Without proper skin care techniques, your hands may start to show signs of aging. Well share some of the causes of aging skin ...
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more ...
... investigation of the genetic and molecular mechanisms that underlie diminished T-cell activation that both occurs in the aging ... T-Cell Activation In Aging is an ...
Swiss anti-aging cream Prestige Cell with a potent and proven ... Swiss anti-aging cream Prestige Cell with a potent and proven ... Prestige Cell not only helps to fight pesky fine lines, wrinkles, creases and crows feet but also works to keep the skin ... This active anti-aging cream is nutrient rich and concentrated to efficiently reduce the appearance of fine lines, wrinkles and ... aging while helping to improve the texture of damaged skin. Prestige Cell is considered highly effective in restoring ...
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As they report in the European Respiratory Journal, they have already successfully counteracted this mechanism in the cell ... Pulmonary fibrosis can possibly be attributed to a kind of cellular aging process, which is called senescence. This has been ... Cell aging in lung epithelial cells. Helmholtz Zentrum München - German Research Center for Environmental Health ... IMAGE: Green cells show markers of the lung epithelium, red cells are undergoing senescence. The nuclei are stained in blue. ...
You see, I have this nagging case of paralysis that makes me passionate about stem-cell policy. I keep hoping President Bush ... I was severely disappointed that President Bush completely ignored embryonic stem-cell research in his State of the Union ... Stem Cell Tactics for a New Age. I was severely disappointed that President Bush completely ignored embryonic stem-cell ... Also, the Domestic Policy Council, which advises Bush on stem-cell policy, released a stem-cell white paper (.pdf) titled ...
Memory T cell homeostasis and senescence during aging.. Akbar AN1, Fletcher JM. ... Human memory T cell pools proliferate and differentiate at varying rates that are determined by the frequency of lifelong ... An important question concerning immunity is whether certain specific pools of memory T cells are driven to exhaustion in ... is an agent that induces specific T cells to extreme differentiation. The question that begs to be answered is whether this can ...
Researchers from The University of Nottingham have demonstrated how a species of flatworm overcomes the aging process to be ... Flatworms Defy Aging Through Cell Division Tricks 106 Posted by Unknown Lamer on Tuesday February 28, 2012 @12:06AM. from the ... Research Council and may shed light on the possibilities of alleviating aging and age-related characteristics in human cells." ... I am wondering now how Humans survive for more than 50 generations, since gametes are also fomred by cell division. ...
Researchers from The University of Nottingham have demonstrated how a species of flatworm overcomes the aging process to be ... Flatworms Defy Aging Through Cell Division Tricks 106 Posted by Unknown Lamer on Tuesday February 28, 2012 @12:06AM. from the ... Research Council and may shed light on the possibilities of alleviating aging and age-related characteristics in human cells." ... Furthermore, cells work together, so if two nearby cells have different lineages then they have different errors, and can ...
Studies in fruit flies have shown how certain cells in the offspring of older fathers can replace copies of genes that have ... Aging Clues Found in Stem Cell Ribosomal DNA. February 14, 2018. 0 ... Their studies looks more closely at the dynamics of rDNA loci and rDNA loss during aging in male Drosophila germline stem cells ... Studies have confirmed that in yeast cells, at least, this rDNA instability and gene copy loss underlies aging, via a process ...
Injecting cardiosphere-derived cells from newborn rats into aged rats hearts rejuvenated heart function, exercise capacity, ... Could stem cells reverse the aging process? Stem cells found in the hypothalamus are responsible for the aging process, new ... Low-calorie diet may slow aging by rejuvenating biological clock Research on how aging alters the way that cells circadian ... What are stem cells and why are they important? Everyones body produces stem cells. They are nonspecific cells that could ...
... as old cells are rejuvenated using resveratrol-like compounds. ... makes a kidney cell a kidney cell and heart cell a heart cell." ... Eradicating mitochondria from cells may reverse aging Scientists found that removing mitochondria from human cells reduced ... to aging human cells and found that they reactivated these splicing factors. This, in turn, not only made the old cells appear ... Anti-aging peptide recovers fur growth, kidney health in mice New study reveals how a peptide targeted senescent cells - known ...
... as old cells are rejuvenated using resveratrol-like compounds. ... makes a kidney cell a kidney cell and heart cell a heart cell." ... Eradicating mitochondria from cells may reverse aging Scientists found that removing mitochondria from human cells reduced ... Macrophages, the immune cells that eat pathogens and cell debris, are often ineffective against cancer cells. How can we co- ... to aging human cells and found that they reactivated these splicing factors. This, in turn, not only made the old cells appear ...
... Jeanne Beck jbeck at Thu Aug 10 11:57:17 EST 2000 *Previous message: ...
New research shows that eating a vegetable-rich diet while exercising and managing stress may help modify cell aging. ... New research shows that eating a vegetable-rich diet while exercising and managing stress may help modify cell aging. ... Further, many cells, such as liver and kidney cells cant lengthen telomeres, while cancer cells can increase telomere length. ... New research showed that eating a diet rich in vegetables while exercising and managing stress may modify cell aging and ...
Mice minus these aged or senescent cells went on to enjoy better kidney function and ... middle-aged mice caused the rodents to live longer, healthier lives, said a study Wednesday that raised intriguing prospects ... Zapping worn-out cells in the organs of ... Zapping worn-out cells in the organs of "middle-aged" mice ... A future step in research would be to test the method on already aged mice, to see if removing senescent cells can reverse age- ...
Cardiac stem cells from young hearts helped reverse the aging process when infused into the old hearts of elderly rats, a study ... Experts in the field of regenerative medicine believe one of the first areas of success when using stem cell-derived therapies ... Unexpected fountain of youth found in cardiac stem cells, says researcher. By Susan Scutti, CNN ...
Tissues with high rates of cell turnover depend on the functional capacity of stem cells for lifelong maintenance of tissue ... ... Adult stem cells are present in most postnatal tissues of mammals. ... Stem cells are the most long-lived cells in the proliferative compartment of mammalian tissues. Therefore, stem cells have an ... Advances in Stem Cell Aging ISBN: 978-3-318-02170-7 e-ISBN: 978-3-318-02171-4 DOI:10.1159/isbn.978-3-318-02171-4 VIII + 126 p ...
In search for mechanisms of cell aging I found only articles and reviews , that were related to cell aging in context of the ... aging of individual cells. JustaPhD justaphd at Wed Jun 17 08:18:00 EST 1998 *Previous message: aging of individual ... Why does a gut epithelium cell live shorter than a liver cell? , What are the mechanisms in aging of one single liver ( ... epithelium, etc.) , cell in both the young child and the old man? , Why (=How) are elderly erythrocytes detected to be removed ...
... according to UC San Francisco researchers who found in a new study that drinking sugary drinks was associated with cell aging. ... Sugared soda consumption, cell aging associated in new study UCSF scientists find shorter telomeres in immune cells of soda ... Sugared soda consumption, cell aging associated in new study. University of California - San Francisco ... according to UC San Francisco researchers who found in a new study that drinking sugary drinks was associated with cell aging. ...
Polycomb group proteins in hematopoietic stem cell aging and malignancies.. Klauke K1,2, de Haan G3,4. ... Department of Cell Biology, Section of Stem Cell Biology, University Medical Center Groningen, University of Groningen, A. ... Department of Cell Biology, Section of Stem Cell Biology, University Medical Center Groningen, University of Groningen, A. ... In this review, we speculate that PcG proteins balance HSC aging against the risk of developing cancer, since a disturbance in ...
  • According to their findings, it is possible to track male GSCs labeled with lacZ gene in Drosophila model by inducing recombination with heat shock and observe the decrease in GSC number with aging. (
  • Heat shock is used to induce Flp recombinase marker gene expression is activated in dividing cells due to recombination. (
  • Consequently, all clone of cells derived from GSC are marked with a functional lacZ gene. (
  • We're learning more and more that dealing with aging is not a black and white issue of 'turn on that gene' or 'turn off that one. (
  • Endothelial progenitor cells (EPCs) as gene carrier system for rat model of human glioma," PLoS ONE , vol. 7, no. 1, Article ID e30310, 2012. (
  • The advances in pluripotent stem cell and gene editing techniques have opened a new avenue to study the pathogenesis of human premature aging syndromes and aging-related diseases (Fu et al. (
  • Both of these facts-that Sox4 is expressed only in some cells in the adult organism, and that it favours cancer development when there is too much of it-indicate that Sox4 is a powerful gene, with important consequences if it is not properly regulated. (
  • BUFFALO, N.Y. -- The fountain of youth may reside in an embryonic stem cell gene named Nanog. (
  • Not only does Nanog have the capacity to delay aging, it has the potential in some cases to reverse it," says Andreadis, noting that the embryonic stem cell gene worked in three different models of aging: cells isolated from aged donors, cells aged in culture, and cells isolated from patients with Hutchinson-Gilford progeria syndrome. (
  • Use these social-bookmarking links to share Blocking gene forces cancer cells to age . (
  • Combining gene editing and stem-cell induction improves efficiency of functional genetic analyses. (
  • We were thus able to pinpoint gene activity in the individual lung cells and ascribe it to the changes in the corresponding gene products - i.e. to the proteins," Dr. Schiller explains. (
  • Whereas in younger lungs a particular cell type will control the gen activity very precisely, the gene activity of older lung cells, and thus also their identity, is less constant," Herbert Schiller explains. (
  • The scientists are working on the assumption that cells lose epigenetic control during the aging process, which results in different gene activities. (
  • The promoter for the Sdpr gene was determined to be progressively hypomethylated with age. (
  • This occurred concurrently with an increase in gene expression with age. (
  • As a result, the p16 gene glows in areas of the body where the gene is active-the more cells expressing the gene, the more intense the glowing effect. (
  • The first mutation found to increase longevity in an animal was the age-1 gene in Caenorhabditis elegans. (
  • The age-1 gene encodes the catalytic subunit of class-I phosphatidylinositol 3-kinase (PI3K). (
  • A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility" (PDF). (
  • In spite of their structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in control of the G1 phase of the cell cycle. (
  • On one end, the hypermethylation, mutation, or deletion of p16 leads to downregulation of the gene and can lead to cancer through the dysregulation of cell cycle progression. (
  • Mutations resulting in deletion or reduction of function of the CDKN2A gene are associated with increased risk of a wide range of cancers and alterations of the gene are frequently seen in cancer cell lines. (
  • LAM involves lung tissue infiltration with smooth muscle-like cells with mutations of the tuberous sclerosis complex gene (TSC2). (
  • Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. (
  • RNA interference (RNAi) is a natural process used by cells to regulate gene expression. (
  • In the four tissue sections shown here, many of the intestinal glands have cells with a mitochondrial DNA mutation in the CCOI gene and appear mostly white, with their main color being the blue-gray staining of the nuclei. (
  • Recent studies have however shown that TFH have distinct gene expression profiles, supporting the theory that TFH are a subset of CD4+ T cells distinct from Th-1, Th-2, Th-17 or Tregs. (
  • There is also a minor sub-class within this population of GC Tfh cells that express the gene Foxp3, encoding for a transcription factor. (
  • The protein encoded by this gene is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation[citation needed]. (
  • Nicotinamide phosphoribosyltransferase (NAmPRTase or Nampt) also known as pre-B-cell colony-enhancing factor 1 (PBEF1) or visfatin is an enzyme that in humans is encoded by the NAMPT gene. (
  • miR16 has been shown to bind to a nine base pair to a complementary sequence in the 3' UTR region of BCL2, which is an anti-apoptotic gene involved in an evolutionarily conserved pathway in programmed cell death. (
  • In humans, telomeres limit cells to ~50 divisions, which is probably related to how DNA replication is only 99.9998% accurate. (
  • Telomeres also help divvy-up the workload among stem cells so the most eager doesn't monopolize the work. (
  • One of the features they mention is the progressive shortening, as cells divide, of telomeres, which are the "caps" that protect the ends of chromosomes. (
  • The researchers explain that "critical shortening" of telomeres is associated with a number of heart problems that arise with age, such as heart dysfunction. (
  • Further, many cells, such as liver and kidney cells can't lengthen telomeres, while cancer cells can increase telomere length. (
  • The good news is that the telomeres in almost all the cells other than WBCs and stem cells do not increase, for if they did, dying of cancer would be all but certain. (
  • Choosing a diet that encourages proper level of leptin and insulin in your body, and thereby proper genetic expression, is likely the most powerful anti-aging diet there is - and may also be involved, or at the very least associated, with the length of your telomeres, although this is only beginning to be explored. (
  • The study revealed that telomeres -- the protective units of DNA that cap the ends of chromosomes in cells -- were shorter in the white blood cells of survey participants who reported drinking more soda. (
  • The length of telomeres within white blood cells -- where it can most easily be measured -- has previously been associated with human lifespan. (
  • Short telomeres also have been associated with the development of chronic diseases of aging, including heart disease, diabetes, and some types of cancer. (
  • The UCSF researchers measured telomeres after obtaining stored DNA from 5,309 participants, ages 20 to 65, with no history of diabetes or cardiovascular disease, who had participated in the nation's largest ongoing health survey, called the National Health and Nutrition Examination Survey, during the years 1999 through 2002. (
  • In a small study involving 35 men in their 50s and 60s, researchers at the Preventive Medicine Research Institute and the University of California, San Francisco found that the 10 participants who adopted several healthful lifestyle changes for five years experienced a 10 percent lengthening of their cell's telomeres, indicating that the cells would have a longer lifespan. (
  • The 25 men in a control group had a 3 percent shortening of their cell's telomeres over five years, which typically occurs during that aging time frame. (
  • Telomeres are "caps" on the ends of chromosomes that facilitate cell replication. (
  • Aging and disease results when telomeres break off. (
  • In probing the links between depression and physical disease, the research team explored aging of the immune system as measured by the shortening of telomeres in immune cells taken from the blood. (
  • Telomerase helps repair and restore telomeres, protecting cells from damage related to premature aging. (
  • During cell replication, the telomeres function by ensuring the cell's chromosomes do not fuse with each other or rearrange, which can lead to cancer. (
  • As is the length of telomeres, the protective end caps of DNA, and of course, stem cells. (
  • Age how you eat: Adopting a diet rich in vegetables and unprocessed foods and focusing on stress-management activities such as yoga have been shown to increase the length of telomeres, the ends of chromosomes linked to aging. (
  • Adopting a diet rich in unprocessed foods combined with moderate exercise and stress management over five years increased the length of telomeres, the ends of chromosomes linked to aging, according to a study of 35 men published in the Lancet medical journal. (
  • He was inspired by Blackburn's research showing that the shortening of telomeres, and therefore aging, is accelerated by emotional stress such as that experienced by women who have parents with Alzheimer's disease or children with autism. (
  • As telomeres become shorter, cells age and die more quickly. (
  • This is the first research to show that exercise can prevent the shortening of telomeres due to stress and buffer the effects of stress-induced cell aging. (
  • Telomerase repairs and lengthens telomeres, which are DNA-protein complexes at the end of chromosomes that directly affect how quickly cells age. (
  • As telomeres become shorter and their structural integrity weakens, cells age and die more quickly, according to background information in a University of California, Irvine, new release. (
  • Your telomeres - protective caps on the ends of your chromosomes, regulators of planned cell death - grow shorter as you age, and this (most likely) leads to cancer . (
  • However, with regards to cellular replication, the progressive shortening of telomeres is a mechanism which limits the amount of generations of a single cell may undergo. (
  • The role of telomeres and telomerase in cell aging and cancer was established by scientists at biotechnology company Geron with the cloning of the RNA and catalytic components of human telomerase and the development of a polymerase chain reaction (PCR) based assay for telomerase activity called the TRAP assay, which surveys telomerase activity in multiple types of cancer. (
  • Telomerase replaces short bits of DNA known as telomeres, which are otherwise shortened when a cell divides via mitosis. (
  • In baboon skeletal muscle, which consists of fully differentiated post-mitotic cells, less than 3% of myonuclei contain damaged telomeres and this percentage does not increase with age. (
  • TA-65 was shown to improve biological markers associated with human health span through the lengthening of short telomeres and rescuing of old cells, although the significance of these findings in actual life expectancy is unknown. (
  • It has been proven that telomeres have an implication in the aging process, and in C. elegans the lifespan - extending effect of long telomeres is dependent on DAF-16. (
  • Dr. Ron Rosedale, M.D. is widely considered to be one of the leading anti-aging doctors in the US, and as such is highly qualified to discuss the complex issues behind using telomere length as an indicator of lifespan. (
  • Getting wrinkles is far more correlated, and is therefore a far better biomarker for aging than telomere length, however undergoing a dermabrasion is not likely to extend lifespan. (
  • The aging and lifespan of normal, healthy cells are linked to the so-called telomerase shortening mechanism, which limits cells to a fixed number of divisions. (
  • Several years ago, during the course of our studies on lysosomes in aging human diploid cells, we observed a small but consistent increase in the lifespan of cultures grown in the presence of 14μM hydrocortisone (HC). (
  • Prolongation of postmitotic lifespan of primary human amnion cells in vitro by hydrocortisone. (
  • The relationship between functional aging, susceptibility to aging-related disease and lifespan itself are explored in two studies in C. elegans , the first examining the role of dietary restriction and reduced insulin signalling in cognitive decline and the second profiling aggregation of the proteome during aging. (
  • Validated biomarkers of aging would allow for testing interventions to extend lifespan, because changes in the biomarkers would be observable throughout the lifespan of the organism. (
  • Although maximum lifespan would be a means of validating biomarkers of aging, it would not be a practical means for long-lived species such as humans because longitudinal studies would take far too much time. (
  • Ideally, biomarkers of aging should assay the biological process of ageing and not a predisposition to disease, should cause a minimal amount of trauma to assay in the organism, and should be reproducibly measurable during a short interval compared to the lifespan of the organism. (
  • as well as Maria Blasco in the journal Aging Cell, finding no increase in murine median or mean lifespan but some physiological anti-aging effects without augmenting cancer incidence. (
  • In a number of species calorie restriction without malnutrition may slow the biological aging process, resulting in longer maintenance of youthful health and an increase in both median and maximum lifespan. (
  • Mutants in this pathway age slower and have a lifespan up to twice as long as normal. (
  • One explanation for the limitation in cell replication is based on the importance of the end-piece, or telomere, of a chromosome. (
  • Cancerous cells reacquire the embryonic ability to reconstruct the telomere, and thus become immortal. (
  • It has been suggested, not without controversy, that increasing telomere length slows down or even reverses aging. (
  • However, it may be possible that the modifications in cell aging being attributed to telomere length increases may actually be a byproduct of healthy genetic expression gained by eating a whole-food, low-sugar diet. (
  • It could very well be, and in fact is likely, that reduced telomere length is a byproduct of the cell damage and turnover associated with aging, rather than a prime cause of it, though it likely does have some adverse repercussions especially to the immune system and possibly stem cells. (
  • This effect on telomere length is comparable to the effect of smoking, or to the effect of regular exercise in the opposite, anti-aging direction, according to UCSF postdoctoral fellow Cindy Leung, ScD, from the UCSF Center for Health and Community and the lead author of the newly published study. (
  • Cells were rejuvenated when the modified stem cells enhanced activity of an enzyme called telomerase, which elongates telomere length. (
  • There is no doubt that stem cells can be used to counter the aging process of cardiac cells caused by telomere degradation," Mohsin said. (
  • however, individuals with nine or more years of untreated chronic depression showed significant telomere shortening, even after accounting for chronological age. (
  • Telomere shortening also was associated with higher levels of inflammation and oxidative stress in patients, both linked to cell damage and premature aging. (
  • The authors suggest that telomere shortening in very chronic depression may reflect an individual's cumulative exposure to biochemical stressors that promote cell death and increase the likelihood of physical disease. (
  • Extracts from Ashwagandha root may significantly increase telomerase activity, thereby protecting against telomere loss and potentially delaying aging, suggest new results from a cell study. (
  • Telomerase is a ribonucleoprotein that can arrest such telomere loss, and therefore offers a pathway to ameliorate the effects of age. (
  • Based on a screen of a number of chemicals, here we found that Vitamin C exerts most efficient rescue for many features in premature aging as shown in WRN-deficient MSCs, including cell growth arrest, increased reactive oxygen species levels, telomere attrition, excessive secretion of inflammatory factors, as well as disorganization of nuclear lamina and heterochromatin. (
  • Immune cells, taken from blood samples, were then examined for telomere length. (
  • To our knowledge, we have reported here the first longitudinal study showing that comprehensive lifestyle changes--or any intervention--are significantly associated with increases in cellular telomerase activity levels and telomere maintenance capacity in immune system cells,' the study authors wrote. (
  • SIRT6 functions in multiple molecular pathways related to aging, including DNA repair, telomere maintenance, glycolysis and inflammation. (
  • The existence of a compensatory mechanism for telomere shortening was first found by Soviet biologist Alexey Olovnikov in 1973, who also suggested the telomere hypothesis of aging and the telomere's connections to cancer. (
  • In humans, skeletal muscle telomere lengths remain stable from ages 23 -74. (
  • Cells can also be induced to senesce via DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes and cell-cell fusion, independent of telomere length. (
  • Although they have protective mechanisms, they still age and lose function. (
  • What are the mechanisms in aging of one single liver (epithelium, etc. (
  • Still, the study expands what is known about the basic molecular and cellular mechanisms of aging - a necessary step to one day designing rational approaches to aiding a healthy aging process. (
  • Simple model systems have played an important role in the discovery of fundamental mechanisms of aging. (
  • These age-related differences may affect the ability of older donor cells to migrate extensively, provide trophic support, persist long-term and promote repair mechanisms,' said Bruce Bunnell, Ph.D., of Tulane University's Center for Stem Cell Research and Regenerative Medicine. (
  • Understanding the molecular and cellular mechanisms involved is critical for developing approaches to attenuate stem cell aging and could pave the way for improved quality of life among the elderly. (
  • General mechanisms of stem cell aging (overview). (
  • Mechanisms of Stem Cell Aging in Model Organisms. (
  • This annual review focuses on invertebrate model organisms, which continue to yield fundamental new insights into mechanisms of aging. (
  • From that information, they hoped to determine the biological age of individuals more accurately using their cells, in contrast to previous studies, which makes use of gross physiology, or examining cellular mechanisms such as DNA methylation. (
  • There has been some evidence to suggest that free radicals and some reactive nitrogen species trigger and increase cell death mechanisms within the body such as apoptosis and in extreme cases necrosis. (
  • Specifically, while the evolutionary trade-off between growth and aging has been well established, the relationship between reproduction and aging is still without scientific consensus, and the cellular mechanisms largely undiscovered. (
  • She has received several awards for her work, including an Ellison Medical Foundation Senior Scholar Award and the Glenn Award for Research in Biological Mechanisms of Aging. (
  • Though both nitric oxide (NO) and hydrogen sulfide have been shown to relax blood vessels, their mechanisms of action are different: while NO activates the enzyme guanylyl cyclase, H 2S activates ATP-sensitive potassium channels in smooth muscle cells. (
  • constitutive activity occurs mainly at the cell surface and is independent of regulatory mechanisms inside the cell, while regulated activity occurs mainly in the golgi and is dependent on the activity of protein kinase C. Alpha-secretase activity in the golgi is thought to compete directly with the beta-secretase pathway for APP substrates during membrane protein maturation. (
  • They showed that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, in vivo or in vitro, uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo. (
  • Vinciguerra unraveled important cellular signaling and epigenetics mechanisms involved in metabolic and infectious processes, stress and aging in the heart and in the liver, such as PI3K/AKT/mTOR pathway and sirtuins, using a systems biology approach in cells and rodent models. (
  • In response to DNA damage NDRG1 translocates from the cytoplasm to the nucleus, where it may inhibit cell growth and promote DNA repair mechanisms. (
  • The research professor of reproductive biology at Stanford University keeps the cells warm and moist deep inside the Lorry I. Lokey Stem Cell Research Building, one of the nation's largest stem cell facilities. (
  • It was established in 2002 and the editors-in-chief are Peter Adams (University of Glasgow), Adam Antebi (Max Planck Institute for Biology of Ageing), Ana Maria Cuervo (Albert Einstein College of Medicine), Brian Kennedy (Buck Institute for Research on Aging), and John Sedivy (Brown University). (
  • New research published in the journal BMC Cell Biology shows that old human cells can be rejuvenated using chemicals similar to resveratrol, which is a substance found in red wine and dark chocolate. (
  • Heinrich Jasper, assistant professor of biology at the University of Rochester, has won a $900,000 Senior Fellow Award from the Ellison Medical Foundation for his work showing how stress affects stem cell function, leading to symptoms of aging. (
  • We show that the place where HSCs form in the bone marrow loses osteopontin upon aging, but if you give back the missing protein to the blood-forming cells they suddenly rejuvenate and act younger," says Hartmut Geiger, PhD, study lead investigator at the Institute for Molecular Medicine and Aging Research Center at the University of Ulm , and the Division of Experimental Hematology and Cancer Biology at Cincinnati Children's. (
  • STEM CELLS TRANSLATIONAL MEDICINE (SCTM), published by AlphaMed Press, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. (
  • His main research interest lies in the molecular biology of aging. (
  • I think this is a fantastic piece of work that begins to explain" how adult stem cells age, said linkurl:Leanne Jones,; a stem cell biologist at the Salk Institute, who was not involved in the study. (
  • 2 Glenn Center for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA, and Center for Regenerative Rehabilitation, Veterans Administration Palo Alto Health Care System, Palo Alto, CA 94304, USA. (
  • 0.2) aging-specific differentially methylated regions (aDMRs) were identified, which are surprisingly few considering the profound age-based changes that occur in HSC biology. (
  • The International Journal of Biochemistry & Cell Biology. (
  • Her contributions to the field of the biology of aging were recognized in 2013 by receipt of the Denham Harman Lifetime Achievement Research Award from the American Aging Association, the society's highest honor. (
  • Nature Cell Biology. (
  • Molecular Biology of the Cell. (
  • Strongylocentrotus purpuratus is one of several biomedical research models in cell and developmental biology. (
  • Molecular Cell Biology (7th ed. (
  • Warner came to this conclusion after analyzing human case of Hutchinson's Gilford syndrome and mouse models of accelerated aging. (
  • Also, the Domestic Policy Council, which advises Bush on stem-cell policy, released a stem-cell white paper (.pdf) titled Advancing Stem Cell Science Without Destroying Human Life earlier this month. (
  • Human memory T cell pools proliferate and differentiate at varying rates that are determined by the frequency of lifelong antigenic re-encounter with different specific antigens. (
  • An important question concerning immunity is whether certain specific pools of memory T cells are driven to exhaustion in elderly subjects, a pertinent point in view of increasing human life expectancy. (
  • full text PDF) in the Proceedings of the National Academy of Sciences , is part of a project funded by the Biotechnology and Biological Sciences Research Council and Medical Research Council and may shed light on the possibilities of alleviating aging and age-related characteristics in human cells. (
  • The Immortal Life Cycle of Turritopsis, with diagrams [] __ Inmmortal human cells. (
  • Human DNA replication (in normal cells with no damage) is 99.99999999% accurate (i.e. about 1 mutation per 10^-10 base pairs). (
  • Modified human stem cells helped the signaling and structure of the heart cells, which were biopsied from elderly patients. (
  • While human cells were used, the research was limited to the laboratory. (
  • Modifying aged human cardiac cells from elderly patients adds to the cell's ability to regenerate damaged heart muscle, making stem cell engineering a viable option," Mohsin said. (
  • A single administration of human umbilical cord blood T cells produces long-lasting effects in the aging hippocampus," Age , vol. 35, no. 6, pp. 2071-2087, 2013. (
  • Intravenous administration of human umbilical cord blood-derived AC133+ endothelial progenitor cells in rat stroke model reduces infarct volume: magnetic resonance imaging and histological findings," Stem Cells Translational Medicine , vol. 2, no. 9, pp. 703-714, 2013. (
  • Transplantation of cryopreserved human umbilical cord blood mononuclear cells does not induce sustained recovery after experimental stroke in spontaneously hypertensive rats," Journal of Cerebral Blood Flow & Metabolism , vol. 34, no. 1, pp. e1-e9, 2014. (
  • The Repository has human cell cultures from individuals with aging-related conditions. (
  • The collection also includes specially characterized normal human diploid fibroblast cultures (IMR90 and IMR91) and over 500 skin fibroblast cultures from subjects participating in the NIA-sponsored Gerontology Research Center Baltimore Longitudinal Study of Aging. (
  • In addition, the Aging Cell Repository has human and animal differentiated cell cultures (epithelial, endothelial, and smooth muscle), human mammary epithelial and keratinocyte cell cultures, and fibroblast cultures from animals with different life spans. (
  • The research team is also acquiring samples of human HSCs to see how those cells respond in laboratory tests to Cdc42 expression. (
  • Results published in Advances in Bioscience and Biotechnology ​ ​ indicated that incubating human HeLa cells with the commercially available KSM-66 Ashwagandha root extract led to an enhancement of approximately 45% in telomerase activity at a concentration of 10 to 50 micrograms. (
  • This is the first published study to use a standardized, branded ashwagandha extract that show an anti-aging effect with a telomerase promotion effect in the human cell line. (
  • We have recently developed a novel human WS model using WRN-deficient human mesenchymal stem cells (MSCs). (
  • 2015 ). These findings suggest that epigenetic alterations could underlie human cellular aging, and the "epigenetic aging" can be repressed or reversed under specific context. (
  • Though much more work remains, Yamashita suspects that similar resets might be at work in certain kinds of human cells, including stem cells and cancer cells. (
  • This study in an animal model of MS is the first to demonstrate that fat-derived stem cells from older human donors have less therapeutic effectiveness than cells from young donors,' said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. (
  • Metabolic aspects of aging in diploid human cells. (
  • The serial cultivation of human diploid cell strains. (
  • The limited in vitro lifetime of human diploid cell strains. (
  • Thymidine incorporation as a measure of population age in human diploid cells. (
  • The model was designed to mimic alterations more likely to cause cancer in colon cells over time, potentially providing the framework for measuring such alterations in human lab-grown colon cells to assess cancer risk. (
  • If what we are seeing in these mouse studies occurs in actual human aging, the model will provide much insight into means for preventing and/or intercepting cancer development. (
  • A ) Representative images of Alizarin Red S staining (original magnification ×200) and Oil Red O staining (original magnification ×1,000) in aged human BMSCs transfected with BMNCR plasmid or empty vector (EV) and followed with osteogenic induction or adipogenic induction, respectively. (
  • To battle aging, the human body holds a reservoir of nonspecialized cells that can regenerate organs. (
  • They got a similar effect when they used the Skp2-blocking drug MLN4924 in lab cultures of human prostate cancer cells. (
  • Single-cell genome analyses reveal the amount of mutations a human brain cell will collect from its fetal beginnings until death. (
  • Chronic Myeloid Leukemia and Aging of Hematopoietic Stem Cells (Mouse/Human). (
  • Wound Healing Repair and Aging of Skin Stem Cells (Mouse/Human). (
  • Tests on human and rabbit skin cells showed a drastic and rapid swelling of fibroblasts, which maintain the connection between cells. (
  • The current study is also a pioneering project for the Human Cell Atlas (HCA). (
  • Fabian Theis plays a leading role in this, and Herbert Schiller focuses specifically on lung-related issues within the HCA consortium and has also co-authored the corresponding white paper for the Human Cell Atlas. (
  • In the next phase, the relevant data for human cells will have to be collected and integrated in the project in order to advance progress in basic and applied research. (
  • Specifically, we have examined the effects of aged muscle and systemic niches on key molecular identifiers of regenerative potential of human embryonic stem cells (hESCs) and post-natal muscle stem cells (satellite cells). (
  • We studied human T cells, isolated from blood donors of all ages, to compare mature cytotoxic T cells with naive ones," said Philip Ansumana Hull, graduate student in Ott's lab and one of the first authors of the study. (
  • The epigenetic clock is a promising biomarker of aging and can accurately predict human chronological age. (
  • It is also possible to predict the human chronological age using the transcriptomic aging clocks. (
  • SIRT6 also rescues the decline in base excision repair of aged human fibroblasts in a PARP1 dependent manner. (
  • A single in vitro study on human CD4 and CD8 T cells led to claims that cycloastragenol may activate telomerase, leading to controversial claims for its role in reducing the effects of aging. (
  • Approximately 90% of the human body's total serotonin is located in the enterochromaffin cells in the GI tract, where it is used to regulate intestinal movements. (
  • For instance, multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant adult human stem cells that can self-renew. (
  • hESCs can be generated by SCNT using dermal fibroblasts nuclei from both a middle-aged 35-year-old male and an elderly, 75-year-old male, suggesting that age-associated changes are not necessarily an impediment to SCNT-based nuclear reprogramming of human cells. (
  • Navitoclax may have senolytic properties against some cell types (e.g., human umbilical vein epithelial cells (HUVECs), IMR90 human lung fibroblasts and murine embryonic fibroblasts (MEFs), but not all (e.g., human primary preadipocytes). (
  • Human embryonic stem cells are often grown in fibroblastic growth factor-2 containing, fetal bovine serum supplemented media. (
  • Cells from malignant breast tumors exhibit extreme MTH1 expression compared to other human cells. (
  • Because a cancer cell divides much more rapidly than a normal human cell, it is far more in need of an enzyme like MTH1 that prevents fatal mutations during replication. (
  • Human PMS2 is expressed at very low levels and is not believed to be strongly cell cycle regulated. (
  • Normal human cells however die after about 50 cell divisions in laboratory culture (the Hayflick Limit, discovered by Leonard Hayflick in 1961). (
  • The age of an adult human is commonly measured in whole years since the day of birth. (
  • The length of an axon can be extraordinary: for example, if a pyramidal cell, (an excitatory neuron) of the cerebral cortex were magnified so that its cell body became the size of a human body, its axon, equally magnified, would become a cable a few centimeters in diameter, extending more than a kilometer. (
  • there are about 86 billion neurons and 85 billion "nonneuronal" (glial) cells in the human male brain. (
  • Current research involving glial cells in the human cochlea proposes that these cells are the common precursor to both mature Schwann cells and satellite glial cells. (
  • They found that in young rats, approximately 25 percent of the neural stem cells were actively dividing, but only 8 percent of the cells in middle-aged rats and 4 percent in old rats were dividing. (
  • However, when the team transplanted these stem cells from young animals into a middle-aged one, they slowed aging. (
  • In some studies, low body weight has been associated with increased mortality, particularly in late middle-aged or elderly subjects. (
  • Cardiosphere-derived cells are immature cells that can mature into any of the three major types of heart cell: cardiomyocytes, endothelial cells, and smooth muscle cells. (
  • Endothelial Cell Aging: How miRNAs Contribute? (
  • Endothelial cells (ECs) form monolayers and line the interior surfaces of blood vessels in the entire body. (
  • In addition, in the nasopharyngeal carcinoma cell line, miR-20a and miR-20b has been shown to target the 3' UTR of vascular endothelial growth factor (VEGF) and repress the expression of VEGF, which is an important angiogenic factor. (
  • In physiologic states, vasodilation occurs through the serotonin mediated release of nitric oxide from endothelial cells. (
  • Simvastatin, a statin, stimulates brain vascular endothelial cells to create a beta-amyloid ejector. (
  • In mammalian cells, p97 is predominantly localized to the cytoplasm, and a significant fraction is associated to membranes of cellular organelles such as the endoplasmic reticulum (ER), Golgi, mitochondria, and endosomes. (
  • The factors also somehow wipe off the epigenetic memory of the cell, making them younger. (
  • Recent evidence shows that fundamental changes in the epigenetic status of HSCs might be one of the driving forces behind many age-related HSC changes and might pave the way for HSC malignant transformation and subsequent leukemia development, the incidence of which increases exponentially with age. (
  • Fizzah Aziz Choudry and Mattia Frontini, "Epigenetic Control of Haematopoietic Stem Cell Aging and Its Clinical Implications," Stem Cells International , vol. 2016, Article ID 5797521, 9 pages, 2016. (
  • In general, the risk of cancer increases with age, but if we can shift the epigenetic landscape through lifestyle changes to limit the impact of methylation fluctuations, we might be able to prevent cancer from developing,' says Easwaran. (
  • Diet, high caloric intake and aging-related inflammation are among the factors believed to support the evolution of epigenetic instability as cancers form. (
  • To study the possible involvement of epigenetic changes in somatic stem cell aging, we used murine hematopoiesis as a model system. (
  • Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. (
  • Since embryonic cells are naturally endowed with a pluripotency program, if you then take that embryo and put it in culture, you can establish pluripotent stem cell lines. (
  • In mammals, only the zygote and early embryonic cells are totipotent, while in plants, many differentiated cells can become totipotent with simple laboratory techniques. (
  • Rather, in Drosophila, activation of dFOXO in the gut/fat body or in neuroendocrine cells acts on other organs to promote healthy aging by signaling to other, as-yet-unidentified factors. (
  • All vital organs begin to lose some function as you age during adulthood. (
  • Aging organs slowly lose function. (
  • Organoids are lab- grown cells that clump together and resemble specific normal organs, such as the colon in this case, and can grow indefinitely. (
  • While solid tumors can be removed surgically or treated with chemotherapy or radiation, metastatic cells that have already entered the circulation are capable of opening a passageway through blood vessels in order to spread to various organs throughout the body. (
  • Fresh cell therapy is mainly the use of live animal embryo organs cells which are injected into the patient with the purpose of achieving a revitalizing effect. (
  • The age of a captured fish specimen can be measured by examining growth patterns similar to tree rings on the otoliths (parts of motion-sensing organs). (
  • Follicular B helper T cells (also known as just follicular helper T cells or TFH), are antigen-experienced CD4+ T cells found in the periphery within B cell follicles of secondary lymphoid organs such as lymph nodes, spleens and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5. (
  • Hematopoietic stem cells (HSCs) regenerate the blood system throughout life and maintain homeostasis. (
  • DNA strand breaks accumulate in long term HSCs during aging. (
  • Lig4 deficiency in the mouse causes a progressive loss of HSCs during aging. (
  • CINCINNATI - As people get older so do the hematopoietic stem cells (HSCs) that form their blood, creating an increased risk for compromised immunity and certain blood cancers. (
  • This could mean younger acting HSCs that form healthier blood cells, boosted immunity in older people, and a better defense mechanism against certain cancers, according to study authors. (
  • This includes the presence of smaller numbers of HSCs with greater potential for forming different types of blood cells, which included larger populations of B and T cells and smaller production of myeloid cells. (
  • The authors also saw aged HSCs treated with recombinant osteopontin regain their youthful characteristics and capacity to form different blood-cell types. (
  • (
  • Taken together, this study provides a comprehensive analysis of the genomic properties of young and old mouse HSCs and suggests how changes in the stem cell during aging promotes self-renewal and hinders HSCs' ability to transition into other types of blood cells. (
  • Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. (
  • The paper brings new perspective to what has been a life science controversy - countering what used to be broad consensus that the aging of hematopoietic stem cells (HSCs) was locked in by nature and not reversible by therapeutic intervention. (
  • HSCs are stem cells that originate in the bone marrow and generate all of the body's red and white blood cells and platelets. (
  • It also confirmed that HSCs rejuvenated by targeting Cdc42 do function similarly to young stem cells. (
  • Right now we can only offer medication, heart transplantation or stem cell therapies with modest regenerative potential, but PIM-1 modification offers a significant advance for clinical treatment. (
  • Regenerative EV therapy appears to be promising in ability to overcome limitations many cell therapies have by the exosomes being able to carry and deliver multiple doses and be able to store and administer treatment. (
  • With age, the ability of skeletal muscle to adapt to changing environmental needs, and meet continuous maintenance and regeneration needs diminishes, resulting in a loss of muscle mass, reduced regenerative capacity, and decreased functionality. (
  • In contrast, many species can be considered immortal: for example, bacteria fission to produce daughter cells, strawberry plants grow runners to produce clones of themselves, and animals in the genus Hydra have a regenerative ability by which they avoid dying of old age. (
  • This reduced cohesion causes them to prematurely separate during cell division, creating eggs that don't have the right number of chromosomes - a state called aneuploidy - which usually renders them infertile. (
  • Microtubules normally corral chromosomes to opposite ends of a dividing cell, so that they can be split evenly in two. (
  • Later on, these cells began to look more normal, but the damage has already been done, says Fitzharris - when division is complete, the egg is more likely to have the wrong number of chromosomes. (
  • Swapping the nuclei of young eggs with those from old eggs showed that it is the age of the egg cell itself, and not the chromosomes inside the nucleus, that seems to cause this problem. (
  • Forming correctly arranged microtubules and segregating chromosomes requires energy, so it could be due to ageing mitochondria - the powerhouses of the cell - which are known to produce less energy. (
  • This is due to the accumulation of oxidative damage to DNA by aging and cellular metabolic activity and the shortening of telomeric terminals of chromosomes. (
  • As you age, the amount of mitochondria you have tends to decline. (
  • The bone-produced hormone osteocalcin may reverse age-related memory decline. (
  • An age-related decline in this DRC, amounting to approximately 0.61% per yr occurred in the controls from 20 to 60 yr of age. (
  • The normal decline in DNA repair with increased age may account for the increased risk of skin cancer that begins in middle age, suggesting that the occurrence of skin cancer in the young may represent precocious aging. (
  • The delay in GSC cell cycle in aging flies as a result of centrosome misorientation suggests a mechanism for the decline in sperm production previously indicated in studies of aging animals," Jones said. (
  • In a nutshell, aging and decline is essentially a tradeoff for increased reproductive robustness in youth. (
  • It has been suggested that age-related cognitive decline is due in part not to neuronal death but to synaptic alterations. (
  • has noted that there is a decrease in grey matter volume between adulthood and old age, whereas white matter volume was found to increase from age 19-40, and decline after this age. (
  • It has also been found that the width of sulcus not only increases with age, but also with cognitive decline in the elderly. (
  • Various approaches have been taken to counteract this age-related decline. (
  • There is a notable decline in the total number of phagocytes in aged hosts, coupled with an intrinsic reduction of their bactericidal activity. (
  • A decline in humoral immunity caused by a reduction in the population of antibody producing B-cells along with a smaller immunoglobulin diversity and affinity. (
  • As age advances, there is decline in both the production of new naive lymphocytes and the functional competence of memory cell populations. (
  • Although myeloid cell production does not seem to decline with age, macrophages become dysregulated as a consequence of environmental changes. (
  • After birth, the decline of T-cell function begins with the progressive involution of the thymus, which is the organ essential for T-cell maturation following the migration of precursor cells from the bone marrow. (
  • This capacity to regenerate does not decline with age and may be linked to their ability to make new stem cells from muscle cells on demand. (
  • Thus eIF4G appears to control differential mRNA translation during periods or growth and stress, which may ultimately lead to age related decline. (
  • This phenomenal extract is naturally rich in skin health boosting nutrients and has been found to include many important anti-aging factors including Alpha Hydroxy Acids, Sugar Enzymes, Citric Bitartrate and Collagen Fibers. (
  • Strikingly, we found that GSCs in the F1 generation are capable of recovering rDNA copy number in the early ages of adulthood, revealing the likely presence of a mechanism that maintains rDNA copy number through generations," the authors write. (
  • We found at 18 months of age, so after six months of treatment, the treated animals were more exploratory, more active, they had also improvements in kidney function, in heart function. (
  • In investigating these intestinal cells, Jasper found that something was scrambling the chemical signal that tells stem cells when to create a particular kind of new cell. (
  • What he found was a surprise: JNK disrupted the delta-notch communication, which confused the stem cells and led to the malformation and over-production of new cells. (
  • They found that in young rats, the hippocampus contained 50,000 stem cells -- and, significantly, this number did not diminish with aging. (
  • This improved structural organization, increased polarity and restored functionality in the older cells to levels found in young cells. (
  • found that the number of Krt-15-GFP-positive (GFP + ) hair follicle stem cells increased with age. (
  • We found that, in vitro, the stem cells from the older donors failed to ameliorate the neurodegeneration associated with EAE. (
  • In the first series of experiments, his team found that these stem cells, which line a V-shaped region of the hypothalamus, disappear as an animal ages. (
  • New research might have found the answer to such questions, and it lies in our wrinkles - not the ones lining our faces, but the ones in our cells. (
  • We found that beta cells turnover up to about age 30, and there they remain throughout life,' said Bruce Buchholz, who led the study. (
  • The typical secretory cell-endocrine cells like those found in the adrenal gland or in the pancreas, as well as nerve cells that secrete neurotransmitters-is filled with tens of thousands of bubble-like vesicles. (
  • The vesicles form by budding off from the cell s golgi apparatus, an organelle found deep in the cell s cytoplasm. (
  • In linkurl:previous work,; Yamashita found that the position of centrosomes -- the organizing centers for microtubules during cell division -- governed asymmetric cell division. (
  • I have only found one clinical study that demonstrates that the chemical 2-dimethyl-amino-ethanol (dimethylaminoethanol), commonly listed in many anti-aging cosmetics as DMAE, may cause a seriously negative reaction in skin cells. (
  • We found that as you grow older, your T-cells capable of recognizing some of the viruses that you haven't encountered before become progressively lower in affinity. (
  • Cancer research is another broad area within which many groups can be found working to understand and control our cells. (
  • An article in the July 2012 issue of Consumer Reports found that 6 out of 10 parents of children aged 8 to 12 have provided their children with cell phones. (
  • A study commissioned in 2012 by John Breyault, Vice President of Public Policy, Telecommunications and Fraud at the National Consumers League found that nearly 60 percent of parents said they offered cell phones to their children at ages 10 or 11.What age is a right age? (
  • They found that naive T cells have a high concentration of SIRT1. (
  • Dr. Cai and his colleagues found that the hypothalamic stem cells appear to exert their anti-aging effects by releasing molecules called microRNAs (miRNAs). (
  • CT scans have found that the cerebral ventricles expand as a function of age. (
  • Certain language functions such as word retrieval and production were found to be located to more anterior language cortices, and deteriorate as a function of age. (
  • The study found SIRT6 was shown to act as a tumor suppressor that blocks the Warburg effect in cancer cells. (
  • most of the DNA can be found in the cell nucleus and, in plants and algae, also in plastids such as chloroplasts. (
  • Homozygous deletion of p16 are frequently found in esophageal cancer and gastric cancer cell lines. (
  • The small study (using T-cells taken from 6 participants) found that TA-65 activated telomerase in cultured cells in all samples, while another Astragalus extract did not. (
  • In the adult subgranular zone (SGZ), dense clusters of dividing cells were found to be anatomically close to the vasculature, especially capillaries. (
  • They are uniquely found predominantly at the border of the T cell zone that merges with the B cell follicles and germinal centers. (
  • Stem-cell niche refers to a microenvironment, within the specific anatomic location where stem cells are found, which interacts with stem cells to regulate cell fate. (
  • Specifically, another study found that MTH1 inhibition in cancer cells leads to incorporation of 8-oxo-dGTP and other oxidatively damaged nucleotides into the cell's DNA, damaging it and causing cell death. (
  • One study found that in animals aged 4-192 years, antioxidant enzymes declined rapidly in the first 25 years, which includes the growth and sexual maturity stages, but afterwards remained stable for over 150 years. (
  • East Asian age reckoning is different from that found in Western culture. (
  • These cells are found in all regions of the brain and spinal cord. (
  • Karyotyping of chromosome structures from individuals with B-cell chronic lymphocytic leukaemias (B-CLL) found that more than half have alterations in the 13q14 region. (
  • Another study in a mouse model shows that stem cells do age and their aging can lead to heart failure. (
  • Recently, a small study published in the Lancet once again confirmed that eating a diet rich in vegetables while exercising and managing stress may modify cell aging and potentially help you live longer. (
  • Epel is co-leading a new study in which participants will be tracked for weeks in real time to look for effects of sugar-sweetened soda consumption on aspects of cellular aging. (
  • Since patients with heart failure are normally elderly, their cardiac stem cells aren't very healthy," said Sadia Mohsin, Ph.D., one of the study authors and a post-doctoral research scholar at San Diego State University's Heart Institute in San Diego, Cal. (
  • Must be used in conjunction with PNAS study on aging. (
  • Safety and biodistribution study of bone marrow-derived mesenchymal stromal cells and mononuclear cells and the impact of the administration route in an intact porcine model," Cytotherapy , vol. 17, no. 4, pp. 392-402, 2015. (
  • Results of the study appear online in the journal Neurobiology of Aging. (
  • The common assumption had been that the brain drain was due to a decreasing supply of neural stem cells in the aging hippocampus, said lead study investigator Bharathi Hattiangady, Ph.D., research associate in neurosurgery. (
  • DNA repair and aging in basal cell carcinoma: a molecular epidemiology study. (
  • This molecular epidemiology study examines the DNA-repair capacities (DRCs) of basal cell carcinoma (BCC) skin cancer patients (88) and their controls (135) by using a plasmid/host-cell reactivation assay. (
  • Most gerontologists (people who study aging) feel that aging is due to the interaction of many lifelong influences. (
  • This study adds to the body of evidence supporting the use of KSM-66 Ashwagandha for anti-aging. (
  • We will review the yeast S. cerevisiae model system with emphasis on the chronological life span as a model system to study aging and the regulation of stress resistance in eukaryotes. (
  • The classic approach to the study of aging in yeast is based on the measurement of replicative life span. (
  • The study is published this week in the journal Cell Reports . (
  • A new study appearing in the latest issue of STEM CELLS Translational Medicine is the first to demonstrate that, in fact, adipose-derived stem cells donated by older people are less effective than cells from their younger counterparts. (
  • This week, a study published in Nature threw a wrench into the classical theory of aging. (
  • Animal cell cultures as a model system for the study of aging. (
  • Comprehensive lifestyle changes, including more fruit and vegetables as well as meditation and yoga, were shown to reverse signs of aging at the cellular level for the first time in a study published Sept. 16. (
  • The nucleus of a cell stores our DNA, explain the authors, and the new study shows the location of our DNA within the nucleus to be of crucial importance. (
  • In the new study, Panagiotis Mistriotis, a graduate student in Andreadis' lab and first author of the study, introduced Nanog into aged stem cells. (
  • This will allow them to study whether aspects of aging inside the body can also be reversed. (
  • The stem cell niche, or microenvironment, helps to maintain stem cell identity by signaling for cell division to be turned on and off, said linkurl:Yukiko Yamashita,; a stem cell scientist at the University of Michigan and lead author of study. (
  • For the current study, we analyzed changes between young and aging lungs down to the single-cell level in a preclinical model," explains Dr. Herbert Schiller. (
  • Our study provides the first such dataset of this magnitude for lung cells," Herbert Schiller explains. (
  • The change was unbelievably obvious," said Dr. Richard T. Lee, a cardiologist at Brigham and Women's Hospital and one of the leaders of the study, published Thursday in the journal Cell . (
  • In the current issue of Nature Biomedical Engineering , lead author Jude M. Phillip, who conducted this research while completing his doctorate in chemical and biomolecular engineering at Johns Hopkins, reports success in creating a system that considers a wide array of cellular and molecular factors in one comprehensive aging study. (
  • We combined some classic biomolecular hallmarks of aging, and sought to further elucidate the role of biophysical properties of aging cells, all in one study," said Phillip, now a post-doctoral fellow at Weill Cornell Medicine. (
  • Life extension strategies often study the causes of aging and try to oppose those causes in order to slow aging. (
  • a separate study demonstrated that SIRT6 overexpression was selectively cytotoxic to cancer cells. (
  • He is a Principal Investigator of the National Institute on Aging funded Long Life Family Study. (
  • The study identified a sequence that can return cells to a 'stem-cell' like state, allowing for better treatment options. (
  • The study of its growth rate and the oxygen isotope data showed that it had a highly variable growth at the peak of the Little Ice Age around 1550-1620 and mild climate near its end around 1765-1780 and had recorded the volcanic eruption of Mount Tambora in 1815. (
  • A young keratinocyte cell is younger than an older keratinocyte but it is still a keratinocyte. (
  • By the time they had reached about 10 days of age, the sons of aged fathers had comparable amounts of rDNA to those male offspring of younger fathers that had passed on less depleted Y chromosomal rDNA. (
  • This, in turn, not only made the old cells appear younger, but they also started dividing again, as young cells would. (
  • Transplantation into the younger animals caused cells to act in a younger more vital manner, the authors report. (
  • When given a young nucleus, older cells still had dysfunctional microtubules, and younger eggs hosting the older nuclei didn't show chaotic cell division. (
  • Small trials using younger donors and elderly recipients hint that mesenchymal stem cell transfers might reduce frailty. (
  • Why, then, would a cell want its younger vesicles to push aside the older ones? (
  • For example, older cells are more rigid and do not move as well as younger cells, which, among other consequences, most likely contributes to the slower wound healing commonly seen in older people, said Denis Wirtz , the senior author, Johns Hopkins' vice provost for research and the Theophilus H. Smoot Professor of Chemical and Biomolecular Engineering at the Whiting School of Engineering. (
  • From the analysis, they were able to stratify individuals' samples into three groups: those whose cells roughly reflected their chronological age, those whose cells were functionally older, and those whose cells were functionally younger. (
  • They were surprised to find a stark difference between the HCV-specific T-cells of older and younger donors. (
  • In fact, HIV-infected patients accumulate mature cyto toxic T cells at a much younger age than an uninfected person. (
  • In other words, aging is not a matter of the increase of damage, but a matter of failure to replace it due to decreased number of stem cells. (
  • Aging of the hair follicle appears to be primed by a sustained cellular response to the DNA damage that accumulates in renewing stem cells during aging. (
  • This damage response involves the proteolysis of type XVII collagen by neutrophil elastase in response to the DNA damage in the hair follicle stem cells. (
  • Jasper knew the enzyme JNK was involved in cell signaling, and that cells activate it to help repair damage when a cell experiences stress, such as from pathogens or injury. (
  • But we can't do away with JNK entirely because it's necessary to help cells fight short-term damage. (
  • Compromised DNA damage responses and the increased production of reactive oxygen species (ROS) have been previously causatively attributed to HSC aging. (
  • New findings indicate that these pathways may have evolved to prevent damage and postpone aging during periods of starvation and may be conserved from yeast to mammals. (
  • What we discovered is if you damage cells, the cells have a built-in mechanism to put themselves out of business," says Pandolfi. (
  • The same mechanism of damage caused by the Sun can be evoked pharmacologically in cancer cells. (
  • Of course, some age-related damage affects all of your cells. (
  • The free radical theory of aging (FRTA) states that organisms age because cells accumulate free radical damage over time. (
  • Noting that radiation causes "mutation, cancer and aging", Harman argued that oxygen free radicals produced during normal respiration would cause cumulative damage which would eventually lead to organismal loss of functionality, and ultimately death. (
  • Such an event causes damage to the molecule, and thus to the cell that contains it (since the molecule often becomes dysfunctional). (
  • Furthermore, in unicellular organisms like Saccharomyces cerevisiae, the formation of extrachromosomal rDNA circles (ERCs) in mother cells (but not daughter cells) upon every subsequent division is an identifiable type of DNA damage that is associated with replication. (
  • The neuroblasts form tight chains and migrate towards the specified site of cell damage to repair or replace neural cells. (
  • While they normally produce digestive fluids for the stomach, they can revert into stem cells to make temporary repairs to stomach injuries, such as a cut or damage from infection. (
  • These findings provide a link between ageing and oxidative DNA damage (see DNA damage theory of aging). (
  • This is consistent with the DNA damage theory of aging. (
  • The DNA damage response (DDR) arrests cell cycle progression until damages, such as double-strand breaks (DSBs), are repaired. (
  • PMS2 is a protective mediator of cell survival in p53-deficient cells and modulates protective DNA damage response pathways independently of p53. (
  • Causes of such memory errors may be due to certain cognitive factors, such as spreading activation, or to physiological factors, including brain damage, age or emotional factors. (
  • The number of stem cells in young people is very much higher than older people and this cause a better and more efficient replacement mechanism in the young contrary to the old. (
  • As they report in the European Respiratory Journal , they have already successfully counteracted this mechanism in the cell culture with the help of drugs. (
  • Whereas FoxO-to-FoxO signaling appears to be required for metabolic homeostasis, our results pinpoint FoxO-to-other signaling as an important mechanism through which localized FoxO activity ameliorates aging. (
  • Ashwagandha deserves to be evaluated as a potential anti-aging ayurvedic herbal preparation in higher organisms and the potential mechanism needs to be investigated. (
  • Ultimately, the aim is to be able to understand and control the mechanism of potency - thus enabling any cell to be transformed into any other type of cell. (
  • This stabilizes an entire mechanism that prevents the cells from entering glycolysis to use sugar as an energy source, and limits their toxic effects. (
  • This leads to alteration of the stem-cell niche and results in stem cell exhaustion, another theorized mechanism of aging. (
  • One proposed mechanism for the observed age-related plasticity deficits in animals is the result of age-induced alterations in calcium regulation. (
  • I was severely disappointed that President Bush completely ignored embryonic stem-cell research in his State of the Union address last night. (
  • The white paper was ostensibly timed to mitigate media excitement over the Stem Cell Research Enhancement Act (SCREA), which passed in the House earlier this month, but not with a veto-proof margin (the same bill was the subject of Bush's first veto last year). (
  • It would allow federal funding for stem-cell research performed using embryos that have been slated for destruction at fertility clinics. (
  • On top of that he will have the white paper and possibly a new executive order to use as a political shield to deflect criticism about his unwillingness to support stem-cell research. (
  • Click through the gallery to learn more about stem cell research. (
  • By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices. (
  • From UCSF Today , an introduction to the way in which cancer research and stem cell research now overlap. (
  • p16 plays an important role in cell cycle regulation by decelerating cells progression from G1 phase to S phase, and therefore acts as a tumor suppressor that is implicated in the prevention of cancers, notably melanoma, oropharyngeal squamous cell carcinoma, cervical cancer, and esophageal cancer. (
  • B-1a cells provide immediate and essential protection from S. pneumoniae through production of natural immunoglobulin, which is germline-like due to minimal insertion of N-region additions. (
  • We have previously demonstrated B-1a derived phosphorylcholine (PC)- specific and total IgM moves away from the germline with age as a result of selection. (
  • In direct contrast, the PtC-binding B-1a cell population preserves its germline status. (
  • They can reprogram themselves to carry out the function of virtually any other type of cell, and play a vital role in early development. (
  • My hypothesis is that we can induce cellular rejuvenation without changing the function of the cells. (
  • The function of a liver cell is to metabolize. (
  • Reprogramming that function means that you no longer have a liver cell. (
  • You now have another cell, which has a totally different function. (
  • The amazing thing is that if you take an aged cell that is fully committed to a certain function, and you transplant its nucleus into an immature egg cell called an oocyte, then you revert its function to a pluripotent, embryonic one, which means it can become any other cell of the body-and you also revert the age of that cell to the youngest age possible. (
  • The treatment improved heart function, increased exercise capacity, and reversed several biomarkers of aging. (
  • The team now is searching for ways to stimulate the brain to replace its own cells in order to improve learning and memory function in the elderly. (
  • Many cells lose their ability to function, or they begin to function abnormally. (
  • But until now, clinical trials of this kind of therapy using elderly patients' own cells have not been a viable option, since aged cells tend not to function as well as cells from young patients. (
  • Aging is associated with reduced organ function and increased disease incidence. (
  • The prominent age-related changes in the appearance, function, and healing properties of skin have been hypothesized to result from changes in epidermal stem cells. (
  • However, the proliferative capacity of these stem cells, which contribute to sebaceous gland function, hair follicle cycling, and wound repair, decreased with age. (
  • Our experiments were originally aimed at testing the idea that, in the specific case of age-related osteoporosis, declining function of osteogenic precursor cells might be at least partially responsible. (
  • Nearly all of them, both professional and commercial, claim to alter the function of the skin to reduce signs of aging. (
  • Many cell phones also give the user access to the internet, email and a camera function, this adds another dimension to the issue of safety. (
  • The cytotoxicity of Natural Killer (NK) cells and the antigen-presenting function of dendritic cells is known to diminish with old age. (
  • Low body weight in the elderly can be caused by pathological conditions associated with aging and predisposing to higher mortality (such as cancer, chronic obstructive pulmonary disorder, or depression) or of the cachexia (wasting syndrome) and sarcopenia (loss of muscle mass, structure, and function). (
  • Yet the niche may also induce pathologies by imposing aberrant function on stem cells or other targets. (
  • Implication in Aging DAF-16 is necessary for dauer formation and the protection of C. elegans during periods of starvation, as DAF-16, DAF-18 and DAF-12 loss - of - function mutants lose the ability to form dauers. (