• Measurements of the length of these telomere strands show that they decrease in length with increasing age, leading many authors to propose that when the length of these telomere strands decreases sufficiently, the cells enter into a state of replicative senescence, eventually leading to disease and death. (ibm.com)
  • There is accumulating evidence that when only a few telomeres are short, they form end-associations, leading to a DNA damage signal resulting in replicative senescence (a cellular growth arrest, also called the M1 stage). (elsevierpure.com)
  • We will argue that telomere shortening in the absence of other alterations may be a potent tumor suppressor mechanism and we will discuss the evidence for and against the major molecular mechanisms proposed to initiate replicative senescence. (elsevierpure.com)
  • While dysfunctional telomeres can block the proliferation of incipient cancer clones by inducing replicative senescence, fusion of dysfunctional telomeres can drive genome instability and oncogenic genomic rearrangements. (telomerescience.com)
  • We demonstrate that PLL provides favourable microenvironment for MSC culture by reversing the replicative senescence. (hindawi.com)
  • Unlike embryonic stem cells, adult stem cells (MSCs) have a limited lifespan and stop proliferating during in vitro culture due to replicative senescence [ 8 ]. (hindawi.com)
  • Moreover, replicative senescence of MSCs exhibits reduced functionality, and cellular senescence might impair the regenerative potential of MSCs [ 10 ]. (hindawi.com)
  • Studies show that replicative senescence or cellular senescence is induced by intrinsic or extrinsic environmental factors [ 11 ]. (hindawi.com)
  • We demonstrate that replicative senescence, a tumor suppressor mechanism and guardian of genome stability, sometimes requires genomic instability to initiate its own action," the authors said. (genengnews.com)
  • Cancer cells overcome this replicative senescence in one of two ways: through activating telomerase, an enzyme that extends telomeres, or using another process called the alternative lengthening of telomeres (ALT) pathway. (massgeneral.org)
  • This phenomenon is termed "replicative senescence" and prevents cells from accumulating too many genetic mutations that may turn them into cancer cells. (scientificamerican.com)
  • Numerous factors localize at telomeres to regulate their length, structure and function, to avert replicative senescence or genome instability and cell death. (cdc.gov)
  • telomere dysfunction and Atm or p53 offers exposed opposing phenotypic outcomes upon lack of Atm versus p53 in the telomerase knockout mouse. (woofahs.com)
  • Outcomes p53 reactivation in cells with telomere dysfunction causes powerful gene manifestation adjustments resembling a mobile checkpoint response To define the p53-mediated transcriptome MSH6 connected with telomere dysfunction, we used a era 4 telomerase-negative, Atm-negative (G4 (triple knockout, TKO) pores and skin fibroblasts display inactivation of mobile checkpoints offering genomic balance. (woofahs.com)
  • Telomeres progressively shorten in almost all dividing cells and most human cells do not express or maintain sufficient telomerase activity to fully maintain telomeres. (elsevierpure.com)
  • Wright, Woodring E. / Senescence and immortalization : Role of telomeres and telomerase . (elsevierpure.com)
  • Blackburn, Carol Greider, and Jack Szostak were awarded the 2009 Nobel Prize in Physiology or Medicine for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase. (wikipedia.org)
  • Integral to this process is telomerase, which is an enzyme that repairs telomeres and is present in various cells in the human body, especially during human growth and development. (asu.edu)
  • Conventional replication leads to telomere shortening, but telomere length is maintained by the enzyme telomerase. (hopkinsmedicine.org)
  • The lab has generated telomerase null mice that are viable and show progressive telomere shortening for up to six generations. (hopkinsmedicine.org)
  • Crosses of these telomerase null mice to other tumor prone mice show that tumor formation can be greatly reduced by short telomeres. (hopkinsmedicine.org)
  • all genes associated with this syndrome (ie, DKC1 , TERT, TERC, NOP10 ) encode proteins in the telomerase complex responsible for maintaining telomeres at the ends of chromosomes regarding shortening length, protection, and replication. (medscape.com)
  • Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. (nih.gov)
  • Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. (nih.gov)
  • Studies in mouse suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. (nih.gov)
  • Telomerase mutations are the most common identifiable genetic cause of IPF, and at times, the telomere defect manifests in extrapulmonary disease such as bone marrow failure. (ersjournals.com)
  • Mutations in the telomerase accessory component, DKC1 , the dyskeratosis congenita 1 gene, can also manifest as IPF, underscoring the important role of telomere dysfunction in IPF pathogenesis [ 10 ]. (ersjournals.com)
  • Mutations in telomerase cause its loss of function and mediate disease through abnormally shortened telomeres [ 11 ]. (ersjournals.com)
  • In contrast to the RNA-directed DNA synthesis by telomerase, ALT relies on recombination and replication of telomere DNA to extend telomeres. (massgeneral.org)
  • Dr. Zou and his team postulated that such cancer cell lines were those without active telomerase, relying instead on the ALT pathway, which lengthens telomeres through recombination with telomeric DNA sequences from the same or other chromosomes. (massgeneral.org)
  • Until now, it had been a riddle to many researchers as to why cultured rodent cells did stop dividing, despite the fact that they have an enzyme called telomerase, which keeps their telomeres at a constant length. (scientificamerican.com)
  • Multi-awarded scientist Elizabeth Blackburn , her student Carol W. Greider and fellow scientist Jack Szostak grabbed the 2009 Nobel Prize in Physiology or Medicine for their discovery of telomeres and the enzyme telomerase. (explorable.com)
  • In December 1984, Greider and Blackburn were able to purify the enzyme that can extend the length of telomeres and they named it telomerase. (explorable.com)
  • With each round of cell division, the length of telomeres is shortened and the enzyme telomerase compensates by maintaining telomere length in germline and stem cells. (medscape.com)
  • Because telomeres function to maintain chromosomal stability, telomerase has a critical role in preventing cellular senescence and cancer progression. (medscape.com)
  • Critically short telomeres activate cellular senescence or apoptosis, as mediated from the tumor suppressor p53, however in the lack of this checkpoint response, telomere dysfunction engenders chromosomal cancer and aberrations. (woofahs.com)
  • Many correlative studies in human cancer and numerous other studies have supported the view that persistent DNA damage signaling resulting from telomere dysfunction provides pressure to deactivate critical checkpoints and sets the stage for 145525-41-3 manufacture accumulation of chromosomal aberrations and aneuploidy [15]. (woofahs.com)
  • Despite the large body of well-described biological outcomes, the molecular mechanisms underlying the role of p53 in suppressing the genomic instability associated with telomere dysfunction are not well understood. (woofahs.com)
  • In this current study, we attempt to dissect the circuitry of the p53-mediated checkpoint response by analyzing transcriptional changes associated with telomere dysfunction. (woofahs.com)
  • In this perspective we will present our views on the evidence for telomere dysfunction in aging and in cancer progression. (elsevierpure.com)
  • Autophagy-independent senescence and genome instability driven by targeted telomere dysfunction. (telomerescience.com)
  • Telomere dysfunction plays a complex role in tumorigenesis. (telomerescience.com)
  • Here, we apply models of acute telomere dysfunction to determine whether autophagy modulates the resulting genome instability and senescence responses. (telomerescience.com)
  • While telomere dysfunction rapidly induces autophagic flux in human fibroblast cell lines, inhibition of the autophagy pathway does not have a significant impact upon the transition to senescence, in contrast to what has previously been reported for oncogene-induced senescence. (telomerescience.com)
  • We also show that chromosome fusions induced by telomere dysfunction are comparable in autophagy-proficient and autophagy-deficient cells. (telomerescience.com)
  • Altogether, our results highlight the complexity of the senescence-autophagy interface and indicate that autophagy induction is unlikely to play a significant role in telomere dysfunction-driven senescence and chromosome fusions. (telomerescience.com)
  • Finally, we discuss how certain hallmarks of ageing (epigenetic alterations, mitochondrial dysfunction, telomere attrition, cellular senescence, and altered intercellular communication) predispose the ageing population to severe COVID-19. (ersjournals.com)
  • In this issue, we generally review the mechanisms of cellular senescence in diabetic nephropathy, which involve telomere attrition, DNA damage, epigenetic alterations, mitochondrial dysfunction, loss of Klotho, Wnt/ β -catenin signaling activation, persistent inflammation, and accumulation of uremic toxins. (hindawi.com)
  • of telomere dysfunction. (hopkinsmedicine.org)
  • In fact, the cell division caused by telomere dysfunction is so unstable that it ends up creating genetic defects. (genengnews.com)
  • His laboratory has developed unique methodologies to analyze telomere dysfunction in multiple tissues using super-resolution microscopy and reporter systems that allow the visualization of telomere damage dynamics in live cells. (mayo.edu)
  • At the cellular level, aging is marked by depletion of adult stem cell reservoirs, the inability to maintain baseline homeostasis, a reduced response to stress, an increased accumulation of damaged DNA leading to telomere shortening, and mitochondrial dysfunction [ 1,2 ]. (karger.com)
  • He had just observed that the ends of the irradiated chromosomes, different from the other genome, did not present alterations such as deletions or inversions, thanks to the presence of a protective cap that he called "terminal gene" and afterwards "telomere", from the greek terms "telos" (end) and "meros" (part) (Müller HJ. (wikipedia.org)
  • Telomeres are non-coding, repetitive sequences located at the termini of linear chromosomes to act as buffers for those coding sequences further behind. (wikipedia.org)
  • Telomeres are sequences of DNA on the ends of chromosomes that protect chromosomes from sticking to each other or tangling, which could cause irregularities in normal DNA functions. (asu.edu)
  • As cells replicate, telomeres shorten at the end of chromosomes, which correlates to senescence or cellular aging. (asu.edu)
  • The study provides insights about the interaction between a toxic protein called progerin and telomeres, which cap the ends of chromosomes like aglets, the plastic tips that bind the ends of shoelaces. (sciencedaily.com)
  • Our current understanding of cellular aging rests upon the uncapping of the repetitive, non-protein-coding extremities of our linear chromosomes called telomeres. (genengnews.com)
  • Telomeres are nucleoprotein complexes at the ends of eukaryotic chromosomes. (biomedcentral.com)
  • Introduction Telomeres, the protective DNA-protein complexes at the end of chromosomes, are required for DNA replication and to protect chromosomes from nuclease degradation, end-to-end fusion, and the initiation of cellular senescence. (lmreview.com)
  • With every division, their telomeres--the ends of their chromosomes--get shorter, providing a molecular clock of sorts that stops their growth after a defined number of doublings. (scientificamerican.com)
  • Telomeres are short fragments of DNA found at the ends of eukaryotic chromosomes. (explorable.com)
  • During the 1930s, Nobel Prize winners Hermann Muller and Barbara McClintock observed that chromosomes are prevented from attaching to each other by a structure found at the ends of the chromosomes, the so-called telomeres. (explorable.com)
  • This mechanism states that the very end of the chromosomes, the so-called telomere, is the one that is not copied during cell division. (explorable.com)
  • Telomeres are short, dense fragments of DNA that can be found at the end of the chromosomes. (explorable.com)
  • This process entails division and replication of chromosomes, and this is where the protective mechanism of the telomeres comes into play. (explorable.com)
  • Objectives: Telomeres are protective DNA sequences on the ends of chromosomes, which can shorten with repeated cell replication and contribute to senescence. (cdc.gov)
  • If aging is not a stochastic process of attrition but is centrally orchestrated, it is reasonable to suspect that the timing of senescence is also influenced by one or more biological clocks. (karger.com)
  • Telomere attrition was also accelerated in cell populations from magnesium-deficient cultures. (wellnessresources.com)
  • TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model. (nih.gov)
  • A recent study demonstrated the molecular basis of tetraploidization by deprotected telomeres in the absence of Pot1 and p53, further implicating dysfunctional telomeres as a cause of genomic instability in human cancer [16]. (woofahs.com)
  • We provide evidence that loss of ZNF365 leads to increased expression of CFS and dysfunctional telomeres, aberrant sister telomere recombination, and increased aneuploidy. (woofahs.com)
  • Dysfunctional telomeres trigger cellular senescence mediated by cyclic GMP-AMP synthase. (bvsalud.org)
  • Dysfunctional telomeres activate DDR signaling, genomic instability , and cellular senescence , but the links among these events remains unclear. (bvsalud.org)
  • Significantly, genetic and pharmacological manipulation of cGAS not only attenuated immune signaling, but also prevented premature cellular senescence in response to dysfunctional telomeres . (bvsalud.org)
  • The researchers have found that short or dysfunctional telomeres activate production of progerin, which is associated with age-related cell damage. (sciencedaily.com)
  • It cannot help in determining the cellular threshold for the number of dysfunctional telomeres that causes cells to stop dividing due to persistent DNA damage response signaling. (genengnews.com)
  • Genetically, we were able to reproduce the phenomenon of cellular aging in the laboratory and ensured that all the telomeres of a population of cells became dysfunctional," said PhD student Marc-Alexandre Olivier, co-first author of the study with former colleague Sabrina Ghadaouia, PhD, currently pursuing postdoctoral studies in England. (genengnews.com)
  • His research has shown that as people age, mitochondria become dysfunctional and produce excessive reactive oxygen species that can accelerate telomere damage, inducing premature senescence. (mayo.edu)
  • In humans, Mendelian defects in several of these factors can result in abnormally short or dysfunctional telomeres, causing a group of rare heterogeneous premature-ageing diseases, termed telomeropathies, short-telomere syndromes or telomere biology disorders (TBDs). (cdc.gov)
  • Methods: Average leukocyte telomere length was estimated by quantitative PCR on a sample of 677 women selected for a study of biomarkers and perceived stress in the NIEHS Sister Study cohort (median age 55, range 35-75). (cdc.gov)
  • Is leukocyte telomere length (LTL) associated with alterations in cardiovascular structure and function? (cdc.gov)
  • In past due era mice and derivative cells, there is certainly improved genomic preservation and instability of p53-mediated senescence and apoptosis, resulting in serious cells degeneration and atrophy, premature ageing, and suppression of cancer compared with controls. (woofahs.com)
  • Recent work has shown that the autophagy pathway regulates both senescence and genome instability in various contexts. (telomerescience.com)
  • The new multistep model for entry into telomere-mediated senescence presented in the current study reconciles observations of senescence-associated genomic instability with observations that telomere breaks are largely irreparable and that cells can tolerate telomere-induced DNA damage foci (TIF) during an unstable "pre-senescent" state. (genengnews.com)
  • They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. (medscape.com)
  • Although the senescent cells remain viable, they show typical changes with enlarged and flattened cell bodies, apoptosis resistance, increased activity of senescence-associated β -galactosidase (SA- β -gal), and upregulation of cyclin-dependent kinase (CDK) inhibitors including p16 INK4A , ARF proteins, and p21 [ 13 - 16 ]. (hindawi.com)
  • Unlike apoptosis, senescence is a state of which cells are still alive and metabolically active. (frontiersin.org)
  • In the later generations, when telomeres are short, cells die via apoptosis or senescence. (hopkinsmedicine.org)
  • Our results suggest that this difference may be explained by disparities in the development of the senescence-associated secretory phenotype. (telomerescience.com)
  • Defective DNA damage response (DDR) signaling is a common mechanism that initiates and maintains the cellular senescence phenotype . (bvsalud.org)
  • Furthermore, senescent cells, with the secretory features known as the senescence-associated secretory phenotype (SASP), could produce proinflammatory cytokines, such as tumor necrosis factor- α (TNF- α ), interleukin-6 (IL-6), and monocyte chemoattractant protein1 (MCP-1), to greatly affect the neighboring cells [ 17 , 18 ]. (hindawi.com)
  • Senescent cells elicit their fibrogenic actions primarily by secreting an assortment of inflammatory and profibrotic factors known as the senescence-associated secretory phenotype (SASP). (frontiersin.org)
  • A novel key feature is the extraction of singleton telomere variant repeats, which improves the identification and subclassification of the alternative lengthening of telomeres phenotype. (biomedcentral.com)
  • The senescence-associated secretory phenotype (SASP) results from the inflammatory, proteolytic and growth factor enriched SECRETOME of many types of senescent cells which leads to tissue repair or tissue and organ damage over time and links SASP to age-related disorders. (bvsalud.org)
  • The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component which serves as a template for the telomere repeat. (nih.gov)
  • Carol Greider , a graduate student, along with her supervisor Blackburn initiated a pioneer study to find out if the formation of telomeres is due to an enzyme. (explorable.com)
  • A common oxidative lesion at telomeres causes rapid premature cellular aging by inducing telomere fragility, rather than telomere shortening. (nature.com)
  • The findings of our study uncover a cellular intrinsic mechanism involving the cGAS-mediated cytosolic self - DNA -sensing pathway that initiates premature senescence independently of telomere shortening . (bvsalud.org)
  • The authors describe these observations about the biology of PTSD as "premature senescence. (medscape.com)
  • Short telomere syndromes are the most prevalent premature aging disorders, with prominent phenotypes affecting the lung and hematopoietic system. (cdc.gov)
  • Of relevance to our study, such genomic fragile sites include telomeres that are particularly sensitive to replication blockade [4, 6]. (woofahs.com)
  • Our study identified ZNF365 as a necessary target whose activation by p53 in the presence of critically short telomeres contributes to genomic stability. (woofahs.com)
  • Other research themes are molecular and genomic ecology, e.g. immune gene evolution, telomere ecology and sex chromosome evolution in birds. (lu.se)
  • We group the hypotheses (i) based on their association with different research questions, and (ii) using a hierarchical approach that builds on the assumptions they make, such as about causality of telomere length/shortening and/or the proposed functional consequences of telomere shortening on organism performance. (lu.se)
  • Our findings argue that senescence acts as a tumor suppressor mechanism that is abrogated during the transition from LGD to HGD in UC. (shengsci.com)
  • In this review, we discuss current understanding of the role and mechanism of cellular senescence in kidney fibrosis. (frontiersin.org)
  • In this review, we summarize the evidence linking cellular senescence to the pathogenesis of CKD and discuss current understanding of the mechanism and regulators controlling senescence. (frontiersin.org)
  • Thus, the long-term consequence of inadequate magnesium availability in human fibroblast cultures was accelerated cellular senescence, which may be a mechanism through which chronic magnesium inadequacy could promote or exacerbate age-related disease. (wellnessresources.com)
  • This mechanism appears to be altered by telomere shortening, and affects protein production for multiple proteins that are important for cytoskeleton integrity. (sciencedaily.com)
  • We here present TelomereHunter, a software for the detailed characterization of telomere maintenance mechanism footprints in the genome. (biomedcentral.com)
  • This result showed a fundamental mechanism involving telomeres that were previously unrecognized. (explorable.com)
  • This mechanism is known as telomere shortening. (explorable.com)
  • The mechanism that limits cell division involves a structure called a telomere. (msdmanuals.com)
  • Furthermore, it was predicted that a specialized DNA polymerase (originally called a tandem-DNA-polymerase) could extend telomeres in immortal tissues such as germ line, cancer cells and stem cells. (wikipedia.org)
  • Systematic analysis of telomere length and somatic alterations in 31 cancer types. (sens.org)
  • Cell cycle-dependent and -independent telomere shortening accompanies murine brain aging. (sens.org)
  • We found that this phenomenon is caused not by telomere shortening , but by cyclic GMP -AMP synthase (cGAS) recognizing cytosolic chromatin fragments and then activating the stimulator of interferon genes ( STING ) cytosolic DNA -sensing pathway and downstream interferon signaling. (bvsalud.org)
  • Tumorigenesis in this setting is associated with telomere shortening that can be observed in the nondysplastic epithelium of UC patients with high-grade dysplasia (HGD) or cancer (UC progressors). (shengsci.com)
  • We hypothesized that a preneoplastic field of inflammation, telomere shortening, and senescence underlies tumor progression in UC progressors. (shengsci.com)
  • In addition, high levels of infiltrating leukocytes were associated with telomere shortening, senescence, and reduced p53 expression. (shengsci.com)
  • Shortening telomeres. (healthnews.com)
  • The slowing down of cell replication occurs due to the shortening of telomeres , which are present at the end of each DNA strand. (healthnews.com)
  • The research suggests that the shortening of telomeres during normal cell division in individuals with normal LMNA genes somehow alters the way a normal cell processes genetic information when turning it into a protein, a process called RNA splicing. (sciencedaily.com)
  • Telomere shortening during cellular senescence plays a causative role in activating progerin production and leads to extensive change in alternative splicing in multiple other genes," said lead author Kan Cao, Ph.D., an assistant professor of cell biology and molecular genetics at the University of Maryland, College Park. (sciencedaily.com)
  • The shortening of telomeres constitutes an intrinsic factor, whereas DNA damage is considered an extrinsic factor. (hindawi.com)
  • Progerin induced senescence, lamin B1 loss, DNA damage, and telomere shortening are prevented by TERT in primary and HGPS fibroblasts, control experiments. (elifesciences.org)
  • In 1973, the Soviet scientist Alexey Olovnikov then predicted the existence of telomere shortening. (explorable.com)
  • Mathematical connection between short telomere induced senescence calculation and mortality rate data for Int. J. Mol. (ibm.com)
  • These ideas are supported by evidence that short telomere length is correlated with increased mortality. (ibm.com)
  • In this paper, we extend this idea to make an actual calculation of the predicted mortality rate caused by short telomere length induced senescence (STLIS). (ibm.com)
  • A team of cancer scientists led by Francis Rodier, PhD, a professor at the University of Montréal, has updated the current model of cellular senescence by providing evidence that the aging-related arrest of DNA replication is caused by irreversible damage to the genome rather than simply by an erosion of telomeres. (genengnews.com)
  • The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence. (sens.org)
  • This telomeric uncapping triggers a continuous DNA Damage Response (DDR) that induces a stable state of cellular senescence accompanied by a complete suspension of cell division. (genengnews.com)
  • Although the current model accepts that telomeric uncapping triggers a telomeric DNA damage response that leads to senescence, the authors showed entry into senescence involves DNA repair mechanisms and a multistep relationship between irreversible telomeric and non-telomeric DNA damage, which control a transient unstable state and a stable state where cell division is arrested. (genengnews.com)
  • We derive a simple equation for the mathematical relationship between telomere length and mortality rate. (ibm.com)
  • Using only three parameters based on telomere length measurement data of Canadians, we have calculated both the magnitude and the age dependence of the mortality rate for both men and women. (ibm.com)
  • Length-independent telomere damage drives post-mitotic cardiomyocyte senescence. (sens.org)
  • Multiple biopsies of varying histologic grade were collected along the colon of nine UC progressors and analyzed for telomere length, DNA damage, senescence, p53, p16, and chronic and acute inflammation. (shengsci.com)
  • Percent body fat, plasma inflammatory markers associated with obesity (interferon (IFN)-γ, interleukin (IL)-10, IL-12 p70, IL-1β, IL-6 and KC/GRO), plasma Cur metabolites and liver telomere length were measured. (springer.com)
  • Minor modulation of telomere length were observed. (springer.com)
  • The effect of Cur and/ or Pip on telomere length in obese mice undergoing CR is not known. (springer.com)
  • To this end, we measured the changes in body weight, area under the curve (AUC) of percent total body fat, telomere length and several markers of inflammation. (springer.com)
  • As such, the mutant gene and mutation type are not the primary mediators of disease severity but the telomere length defect, as previously reviewed [ 11 ]. (ersjournals.com)
  • During repeated cellular division, the length of the telomeres shortens progressively. (explorable.com)
  • Telomere length and work schedule characteristics in the NIEHS sister study. (cdc.gov)
  • Shorter telomere length has been associated with chronic stress , age and obesity in women, and with metabolic and cardiovascular disease outcomes. (cdc.gov)
  • We hypothesised that cumulative lifetime years of full-time and over-time work, rotating shiftwork or irregular hours, may be related to shorter telomere length in women. (cdc.gov)
  • Age-adjusted regression models estimated associations with telomere length. (cdc.gov)
  • Results: Currently holding a full-time job and years of full-time work were significantly associated with shorter telomere length (b =20.003 per year, p = 0.002) independent of the effects of age (b =20.006 per year, p,0.0001). (cdc.gov)
  • Years in jobs characterised as over-time, shift-work and irregular hours were not consistently related to telomere length. (cdc.gov)
  • Conclusion: Telomere length may be associated with lifetime years of fulltime work in some women. (cdc.gov)
  • Is telomere length a key mediator of, or merely correlated with, disease-associated fitness costs? (lu.se)
  • In addition to the mutations that directly effect telomere length, recent studies also indicate that a DKC diagnosis should not be based solely on the length of the telomere, but also the fact that there are defects in telomere replication and protection. (medscape.com)
  • Telomere Length and Clonal Hematopoiesis. (cdc.gov)
  • Our GWAS confirmed 11 genetic loci previously associated with leucocyte telomere length (LTL) and two novel loci in SCNN1D and PITPNM1. (cdc.gov)
  • A recent in vitro study found that prolonged exposure to the proton pump inhibitor (PPI) esomeprazole impaired endothelial function and accelerated human endothelial senescence by reducing telomere length. (medscape.com)
  • Rapidly proliferating tissues with the greatest need for telomere maintenance (eg, bone marrow) are at greatest risk for failure. (medscape.com)
  • Mice have long telomeres and senesce just fine. (cdc.gov)
  • While short telomeres do lead to health problems, long telomeres lead to health problems of their own. (cdc.gov)
  • Far from extending life, long telomeres appear to cause cancer and a blood disorder known as CHIP, a condition that increases the risk of blood cancers and heart disease. (cdc.gov)
  • The processes that maintain telomeres employ replication protein A (RPA), a single-stranded DNA binding protein. (massgeneral.org)
  • Telomeres are important component of cell division that protect the genome DNA against cellular senescence and promote chromosomal stability. (springer.com)
  • Establishment of telomere maintenance mechanisms is a universal step in tumor development to achieve replicative immortality. (biomedcentral.com)
  • For the first time, we determine the correlation of in silico telomere content quantification from whole genome sequencing and whole genome bisulfite sequencing data derived from the same tumor sample (r = 0.78). (biomedcentral.com)
  • However, to precisely identify and interfere with these mechanisms in various tumor types, more insight into the different telomere structures is needed. (biomedcentral.com)
  • Here, we present TelomereHunter, a new computational tool for determining telomere content that is specifically designed for matched tumor and control pairs. (biomedcentral.com)
  • Dr. Zou and his team had previously investigated the role for RPA at telomeres3 and found that it associated transiently with telomeres during S phase of DNA replication. (massgeneral.org)
  • And indeed the team found that in cells that use the ALT pathway, RPA binds persistently to telomeres, not detaching after replication. (massgeneral.org)
  • The study is reported in an article in the journal Nucleic Acids Research, titled, " Homologous recombination-mediated irreversible genome damage underlies telomere-induced senescence . (genengnews.com)
  • Short telomeres and increased DNA damage, senescence, and infiltrating leukocytes were observed in biopsies located less than 10 cm from HGD or cancer. (shengsci.com)
  • Telomeres protect chromosome ends from being recognized as DNA damage and chromosomal rearrangements. (hopkinsmedicine.org)
  • Future work in the lab will focus on identifying genes that induce DNA damage in response to short telomeres, identifying how telomeres are processed and how telomere elongation is regulated. (hopkinsmedicine.org)
  • This updated model offers a new basis for stress- or age-associated genome damage and indicates, cells that escape telomere-mediated senescence harbor irreparable genome damage. (genengnews.com)
  • The model also suggests that strategies targeted at repairing telomeres in pre-senescent cells could eradicate telomere-induced DNA damage foci and low-level DNA damage response while preventing further irreversible damage to the genome. (genengnews.com)
  • His work demonstrates how cellular senescence depends on chronic DNA-damage signaling that results from irreparable damage to telomeres. (mayo.edu)
  • In the present review, we will focus on the role of cellular senescence and its related mechanisms in DN. (hindawi.com)
  • This has resulted in the formulation of a multitude of, often name-given, hypotheses related to the associations between telomeres and life-history traits or fitness-facilitating processes (and the mechanisms underlying them). (lu.se)
  • The mechanisms underlying the cellular senescence of MSCs are still poorly understood. (hindawi.com)
  • Cellular senescence is a complex process, and its molecular mechanisms are unknown. (hindawi.com)
  • TelomereHunter provides new functionality for the analysis of the footprints of telomere maintenance mechanisms in cancer genomes. (biomedcentral.com)
  • His team is currently investigating the mechanisms by which mitochondria drive senescence with the hope of finding new therapies to increase healthspan as adults age. (mayo.edu)
  • Cells age as part of the normal cell cycle process called senescence, which progressively advances through a limited number of divisions in the cell lifetime. (sciencedaily.com)
  • This means that the telomere shortens progressively during cellular division. (explorable.com)
  • Aging kidney and CKD share many common characteristic features with increased cellular senescence, a conserved program characterized by an irreversible cell cycle arrest with altered transcriptome and secretome. (frontiersin.org)
  • Cellular senescence is characterized by an irreversible and permanent cell cycle arrest coupled with altered transcriptome and secretome. (frontiersin.org)
  • Cellular senescence refers to active cells that eventually enter a state of irreversible growth arrest. (hindawi.com)
  • In the absence of cell-cycle checkpoint pathways (e.g. p53 and or p16/Rb), cells bypass M1 senescence and telomeres continue to shorten eventually resulting in crisis (also called the M2 stage). (elsevierpure.com)
  • Stress, cell senescence and organismal ageing. (sens.org)
  • Telomeres and Cell Senescence - Size Matters Not. (sens.org)
  • According to his theory of marginotomy DNA sequences at the ends of telomeres are represented by tandem repeats, which create a buffer that determines the number of divisions that a certain cell clone can undergo. (wikipedia.org)
  • Even though cells replicate to survive, they undergo a process of cellular senescence , where the dividing slows down and the cell eventually "retires. (healthnews.com)
  • However, the telomeres get shorter with each cell division, possibly leading to improper cell division and errors responsible for various age-related illnesses or cancer. (healthnews.com)
  • Telomeres wear away during cell division. (sciencedaily.com)
  • As the telomeres shorten, the cell produces more progerin. (sciencedaily.com)
  • The more cell divisions the cell underwent, the shorter the telomeres and the greater the production of progerin. (sciencedaily.com)
  • Cellular senescence, which is morphologically characterized by an enlarged and flattened cell shape, was first described by Hayflick [ 9 ]. (hindawi.com)
  • The team also showed that this stable stage is preceded by an unstable transient stage when the cell continues to divide despite uncapped telomeres. (genengnews.com)
  • Levels of TERRA fluctuate during the cell cycle as RPA binds and detaches from telomeres. (massgeneral.org)
  • Do the telomeres in cancer cells get shorter each time the cell divides? (scientificamerican.com)
  • Telomeres are used to move the cell's genetic material in preparation for cell division. (msdmanuals.com)
  • Every time a cell divides, the telomeres shorten a bit. (msdmanuals.com)
  • Eventually, the telomeres become so short that the cell can no longer divide. (msdmanuals.com)
  • When a cell stops dividing, it is called senescence. (msdmanuals.com)
  • Many researchers have focused on telomeres, which are composed of a series of TTAGGG repeat nucleotide sequences at the ends of each chromosome. (ibm.com)
  • In 1975-1977, Elizabeth Blackburn, working as a postdoctoral fellow at Yale University with Joseph G. Gall, discovered the unusual nature of telomeres, with their simple repeated DNA sequences composing chromosome ends. (wikipedia.org)
  • While developmental senescence and acute senescence may positively contribute to the fine-tuning of embryogenesis and injury repair, chronic senescence, when unresolved promptly, plays a crucial role in kidney fibrogenesis and CKD progression. (frontiersin.org)
  • Some of our target research questions are: is there a causative link between costs of chronic malaria infection and accelerated senescence of the body? (lu.se)
  • Hidden costs of infection: chronic malaria accelerates telomere degradation and senescence. (lu.se)
  • Analysis of alternative lengthening of telomere markers in BRCA1 defective cells. (sens.org)
  • Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
  • What's most surprising is that, before really entering senescence, the cells divide one last time," said Rodier. (genengnews.com)
  • In this study, we examined whether normal human cells could tolerate telomere uncapping and showed that p53 wild-type diploid cells reacted but rapidly adapted to telomere uncapping," the authors noted. (genengnews.com)
  • Counterintuitively the definition of cellular senescence is of cells that can no longer divide to make two new cells, rather than cells that no longer work. (thenakedscientists.com)
  • Fortunately for us, of the 37 trillion or so cells in our body, only a relatively small amount have undergone senescence. (thenakedscientists.com)
  • The telomere plays a key role in the continuous duplication of proliferating cells, and its erosion eventually leads to a cell's senescence. (massgeneral.org)
  • Joao Passos, Ph.D., investigates the role of senescent cells in aging and age-related disease, with a particular focus on the role of mitochondria and telomeres in the process. (mayo.edu)
  • Consider the study from some years back that showed as many as 20% of the skin cells in old baboons exhibited the signature for senescence. (fightaging.org)
  • Abstract Cellular senescence, although protective when triggered in cells that have become cancerous, plays a key pathological role in other age-associated diseases and in so-called "healthy aging. (lmreview.com)
  • Telomere dynamics are a critical component of both aging and cancer. (elsevierpure.com)
  • Ulcerative colitis-associated colorectal cancer arises in a field of short telomeres, senescence, and inflammation. (shengsci.com)
  • These processes leave molecular footprints in cancer genomes in the form of altered telomere content and aberrations in telomere composition. (biomedcentral.com)
  • To retrieve these telomere characteristics from high-throughput sequencing data the available computational approaches need to be extended and optimized to fully exploit the information provided by large scale cancer genome data sets. (biomedcentral.com)
  • Long non-coding RNAs at work on telomeres: Functions and implications in cancer therapy. (nih.gov)
  • María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and co-author of the study, noted on the institution's website, "The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging. (medscape.com)
  • Less understood are a newly recognized group of cancer-prone syndromes that are associated with mutations that lengthen telomeres. (cdc.gov)
  • A large body of new data from Mendelian genetics and epidemiology now provides an opportunity to reconsider paradigms related to the role of telomeres in human aging and cancer. (cdc.gov)
  • The longer a person's telomeres, researchers found, the greater the risk of cancer and other disorders, challenging a popular hypothesis about the chromosomal roots of vitality. (cdc.gov)
  • Furthermore, Dr. Passos uncovered a key role for mitochondria in the induction of cellular senescence. (mayo.edu)
  • Dr. Passos has identified a key role for mitochondria in cellular senescence. (mayo.edu)
  • It was also shown that inhibition of the p16 tumour suppressor gene delays growth arrest and therefore senescence of MSC [ 16 ]. (hindawi.com)
  • Another gene implicated in DKC, TINF2 , encodes a key component of the protein shelterin, which plays a role in telomere homeostasis. (medscape.com)
  • A heterozygous mutation was found on the conserved telomere maintenance component 1 gene ( CTC1 ). (medscape.com)
  • My research encompasses theoretical, methodological and empirical studies related to various eco-immunological issues such as the identification and quantification of immune costs (both in terms of physiology and Darwinian fitness), direct and long-term (hidden) costs of infection (telomeres and senescence), sexual selection and honest signaling, sexually antagonistic selection (e.g. on immune gene (MHC) diversity and immunity effects of maternal programming (antibody and hormone transfer to offspring). (lu.se)
  • These telomeres act as protective caps, similar to the plastic nib at the end of a shoelace. (healthnews.com)
  • They thought that the telomeres have protective roles in the chromosome but its manner of action was still unknown. (explorable.com)
  • Low-grade dysplasia (LGD) had the shortest telomeres along with the highest levels of senescence and infiltrating leukocytes, whereas HGD biopsies showed the opposite pattern. (shengsci.com)
  • Telomeres Increasingly Develop Aberrant Structures in Aging Humans. (sens.org)
  • Dr. Passos' research has shown that telomeres can sense stress and become irreparably damaged during aging in a variety of tissues and age-related diseases. (mayo.edu)
  • Dr. Passos' research has shown a role for telomere-induced senescence in multiple tissues with aging and age-related diseases. (mayo.edu)
  • Recently, the emerging role of cellular senescence in DN has attracted a broad attention. (hindawi.com)
  • Dyskerin is composed of 514 amino acids and has a role in ribosomal RNA processing and telomere maintenance. (medscape.com)
  • The Role of Telomeres in Human Disease. (cdc.gov)
  • A recent study proposes a key role for telomere maintenance in the development of clonal hematopoiesis. (cdc.gov)
  • The review included 22 studies of senescence-related biomarkers with sufficient information to calculate pooled effect sizes, including six reports on LTL in PTSD. (medscape.com)