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.Caloric Tests: Elicitation of a rotatory nystagmus by stimulating the semicircular canals with water or air which is above or below body temperature. In warm caloric stimulation a rotatory nystagmus is developed toward the side of the stimulated ear; in cold, away from the stimulated side. Absence of nystagmus indicates the labyrinth is not functioning.Longevity: The normal length of time of an organism's life.Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Diet, Reducing: A diet designed to cause an individual to lose weight.Food Deprivation: The withholding of food in a structured experimental situation.Weight Loss: Decrease in existing BODY WEIGHT.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Sirtuins: A homologous family of regulatory enzymes that are structurally related to the protein silent mating type information regulator 2 (Sir2) found in Saccharomyces cerevisiae. Sirtuins contain a central catalytic core region which binds NAD. Several of the sirtuins utilize NAD to deacetylate proteins such as HISTONES and are categorized as GROUP III HISTONE DEACETYLASES. Several other sirtuin members utilize NAD to transfer ADP-RIBOSE to proteins and are categorized as MONO ADP-RIBOSE TRANSFERASES, while a third group of sirtuins appears to have both deacetylase and ADP ribose transferase activities.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Sirtuin 1: A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation.DNA Restriction Enzymes: Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.Obesity: A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).Polymorphism, Restriction Fragment Length: Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.Eating: The consumption of edible substances.Rats, Inbred F344Body Composition: The relative amounts of various components in the body, such as percentage of body fat.Stilbenes: Organic compounds that contain 1,2-diphenylethylene as a functional group.Adipose Tissue: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.Cheirogaleidae: A family of the order PRIMATES, suborder Strepsirhini (PROSIMII), containing five genera. All inhabitants of Madagascar, the genera are: Allocebus, Cheirogaleus (dwarf lemurs), Microcebus (mouse lemurs), Mirza, and Phaner.Fasting: Abstaining from all food.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Diet: Regular course of eating and drinking adopted by a person or animal.Sirtuin 3: A sirtuin family member found primarily in MITOCHONDRIA. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.Mice, Inbred C57BLLeptin: A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.Exercise: Physical activity which is usually regular and done with the intention of improving or maintaining PHYSICAL FITNESS or HEALTH. Contrast with PHYSICAL EXERTION which is concerned largely with the physiologic and metabolic response to energy expenditure.Physical Conditioning, Animal: Diet modification and physical exercise to improve the ability of animals to perform physical activities.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.Peganum: A plant genus of the family ZYGOPHYLLACEAE. Harmala and other ALKALOIDS, phenylpropanoids, and TRITERPENES have been found in plants of this genus.Gastric Bypass: Surgical procedure in which the STOMACH is transected high on the body. The resulting small proximal gastric pouch is joined to any parts of the SMALL INTESTINE by an end-to-side SURGICAL ANASTOMOSIS, depending on the amounts of intestinal surface being bypasses. This procedure is used frequently in the treatment of MORBID OBESITY by limiting the size of functional STOMACH, food intake, and food absorption.Dietary Carbohydrates: Carbohydrates present in food comprising digestible sugars and starches and indigestible cellulose and other dietary fibers. The former are the major source of energy. The sugars are in beet and cane sugar, fruits, honey, sweet corn, corn syrup, milk and milk products, etc.; the starches are in cereal grains, legumes (FABACEAE), tubers, etc. (From Claudio & Lagua, Nutrition and Diet Therapy Dictionary, 3d ed, p32, p277)Hunger: The desire for FOOD generated by a sensation arising from the lack of food in the STOMACH.Feeding Behavior: Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals.Overweight: A status with BODY WEIGHT that is above certain standard of acceptable or desirable weight. In the scale of BODY MASS INDEX, overweight is defined as having a BMI of 25.0-29.9 kg/m2. Overweight may or may not be due to increases in body fat (ADIPOSE TISSUE), hence overweight does not equal "over fat".Deoxyribonucleases, Type II Site-Specific: Enzyme systems containing a single subunit and requiring only magnesium for endonucleolytic activity. The corresponding modification methylases are separate enzymes. The systems recognize specific short DNA sequences and cleave either within, or at a short specific distance from, the recognition sequence to give specific double-stranded fragments with terminal 5'-phosphates. Enzymes from different microorganisms with the same specificity are called isoschizomers. EC 18.104.22.168.Macaca mulatta: A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans.Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Basal Metabolism: Heat production, or its measurement, of an organism at the lowest level of cell chemistry in an inactive, awake, fasting state. It may be determined directly by means of a calorimeter or indirectly by calculating the heat production from an analysis of the end products of oxidation within the organism or from the amount of oxygen utilized.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Dietary Proteins: Proteins obtained from foods. They are the main source of the ESSENTIAL AMINO ACIDS.Adiposity: The amount of fat or lipid deposit at a site or an organ in the body, an indicator of body fat status.Ghrelin: A 28-amino acid, acylated, orexigenic peptide that is a ligand for GROWTH HORMONE SECRETAGOGUE RECEPTORS. Ghrelin is widely expressed but primarily in the stomach in the adults. Ghrelin acts centrally to stimulate growth hormone secretion and food intake, and peripherally to regulate energy homeostasis. Its large precursor protein, known as appetite-regulating hormone or motilin-related peptide, contains ghrelin and obestatin.Oxygen Consumption: The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)Weight Gain: Increase in BODY WEIGHT over existing weight.Azaserine: Antibiotic substance produced by various Streptomyces species. It is an inhibitor of enzymatic activities that involve glutamine and is used as an antineoplastic and immunosuppressive agent.Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Obesity, Morbid: The condition of weighing two, three, or more times the ideal weight, so called because it is associated with many serious and life-threatening disorders. In the BODY MASS INDEX, morbid obesity is defined as having a BMI greater than 40.0 kg/m2.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Blood Glucose: Glucose in blood.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Hypothalamus: Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.Sarcopenia: Progressive decline in muscle mass due to aging which results in decreased functional capacity of muscles.Organ Size: The measurement of an organ in volume, mass, or heaviness.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Life Expectancy: Based on known statistical data, the number of years which any person of a given age may reasonably expected to live.Body Mass Index: An indicator of body density as determined by the relationship of BODY WEIGHT to BODY HEIGHT. BMI=weight (kg)/height squared (m2). BMI correlates with body fat (ADIPOSE TISSUE). Their relationship varies with age and gender. For adults, BMI falls into these categories: below 18.5 (underweight); 18.5-24.9 (normal); 25.0-29.9 (overweight); 30.0 and above (obese). (National Center for Health Statistics, Centers for Disease Control and Prevention)Adaptation, Physiological: The non-genetic biological changes of an organism in response to challenges in its ENVIRONMENT.Insulin-Like Growth Factor I: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.Mitochondria, Muscle: Mitochondria of skeletal and smooth muscle. It does not include myocardial mitochondria for which MITOCHONDRIA, HEART is available.Nystagmus, Physiologic: Involuntary rhythmical movements of the eyes in the normal person. These can be naturally occurring as in end-position (end-point, end-stage, or deviational) nystagmus or induced by the optokinetic drum (NYSTAGMUS, OPTOKINETIC), caloric test, or a rotating chair.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.TriglyceridesRats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Rats, Inbred BNLipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Mice, Obese: Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid.Physical Exertion: Expenditure of energy during PHYSICAL ACTIVITY. Intensity of exertion may be measured by rate of OXYGEN CONSUMPTION; HEAT produced, or HEART RATE. Perceived exertion, a psychological measure of exertion, is included.Starvation: Lengthy and continuous deprivation of food. (Stedman, 25th ed)Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.DNA, Mitochondrial: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.Adenylate Kinase: An enzyme that catalyzes the phosphorylation of AMP to ADP in the presence of ATP or inorganic triphosphate. EC 22.214.171.124.Biomimetic Materials: Materials fabricated by BIOMIMETICS techniques, i.e., based on natural processes found in biological systems.
CALERIE: CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) is a trial currently underway in the U.S.Maximum life span: Maximum life span is a measure of the maximum amount of time one or more members of a population has been observed to survive between birth and death. The term can also denote an estimate of the maximum amount of time that a member of a given species could survive between life and death, provided circumstances that are optimal to their longevity.List of countries by food energy intake: Food consumption refers to the amount of food available for human consumption as estimated by the FAO Food Balance Sheets. However the actual food consumption may be lower than the quantity shown as food availability depending on the magnitude of wastage and losses of food in the household, e.Dieter Weichert: Dieter Weichert (born 1948) is a German mechanical engineer specialising in solid mechanics and polymer rheology. Since 1995 he is the Director of the Institute for General Mechanics of RWTH Aachen.Compensatory growth (organism): Compensatory growth, known as catch-up growth and compensatory gain, is an accelerated growth of an organism following a period of slowed development, particularly as a result of nutrient deprivation. The growth may be with respect to weight or length (or height in humans).Management of obesity: The main treatment for obesity consists of dieting and physical exercise. Diet programs may produce weight loss over the short term, but maintaining this weight loss is frequently difficult and often requires making exercise and a lower calorie diet a permanent part of an individual's lifestyle.Index of energy articles: This is an index of energy articles.Protein deacetylase: Protein deacetylase; any enzyme that removes acetyl groups from lysine amino acids in proteins.Restriction fragment: A restriction fragment is a DNA fragment resulting from the cutting of a DNA strand by a restriction enzyme (restriction endonucleases), a process called restriction. Each restriction enzyme is highly specific, recognising a particular short DNA sequence, or restriction site, and cutting both DNA strands at specific points within this site.Classification of obesity: Obesity is a medical condition in which excess body fat has accumulated to the extent that it has an adverse effect on health.WHO 2000 p.Amplified fragment length polymorphismPRX-07034: PRX-07034 is a selective 5-HT6 receptor antagonist. It has cognition and memory-enhancing properties and potently decreases food intake and body weight in rodents.Vitisin B (stilbenoid): Vitisin B}}Adipose tissue macrophages: Adipose tissue macrophages (abbr. ATMs) comprise tissue resident macrophages present in adipose tissue.Mayo Clinic Diet: The Mayo Clinic Diet is a diet created by Mayo Clinic. Prior to this, use of that term was generally connected to fad diets which had no association with Mayo Clinic.LeptinHigh-intensity interval training: High-intensity interval training (HIIT), also called high-intensity intermittent exercise (HIIE) or sprint interval training (SIT), is an enhanced form of interval training, an exercise strategy alternating short periods of intense anaerobic exercise with less-intense recovery periods. HIIT is a form of cardiovascular exercise.Insulin signal transduction pathway and regulation of blood glucose: The insulin transduction pathway is an important biochemical pathway beginning at the cellular level affecting homeostasis. This pathway is also influenced by fed versus fasting states, stress levels, and a variety of other hormones.Myokine: A myokine is one of several hundred cytokines or other small proteins (~5–20 kDa) and proteoglycan peptides that are produced and released by muscle cells (myocytes) in response to muscular contractions.Bente Klarlund Pedersen , Thorbjörn C.Gastric bypass surgeryCarbohydrate loading: Carbohydrate loading, commonly referred to as carb-loading or carbo-loading, is a strategy used by endurance athletes, such as marathon runners, to maximize the storage of glycogen (or energy) in the muscles and liver.http://www.Hunger (motivational state): Hunger is a sensationOverweight PoochHoming endonuclease: The homing endonucleases are a collection of endonucleases encoded either as freestanding genes within introns, as fusions with host proteins, or as self-splicing inteins. They catalyze the hydrolysis of genomic DNA within the cells that synthesize them, but do so at very few, or even singular, locations.Animal fatLiver sinusoid: A liver sinusoid is a type of sinusoidal blood vessel (with fenestrated, discontinuous endothelium) that serves as a location for the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein.SIU SOM Histology GITemporal analysis of products: Temporal Analysis of Products (TAP), (TAP-2), (TAP-3) is an experimental technique for studyingProtein toxicity: Protein toxicity with proteinuria can result in those with preexisting kidney disease, or those who have lost kidney function due to age.Respirometer: A respirometer is a device used to measure the rate of respiration of a living organism by measuring its rate of exchange of oxygen and/or carbon dioxide. They allow investigation into how factors such as age, chemicals or the effect of light affect the rate of respiration.AzaserineMitochondrion: The mitochondrion (plural mitochondria) is a double membrane-bound organelle found in most eukaryotic cells. The word mitochondrion comes from the Greek , , i.Blood glucose monitoring: Blood glucose monitoring is a way of testing the concentration of glucose in the blood (glycemia). Particularly important in the care of diabetes mellitus, a blood glucose test is performed by piercing the skin (typically, on the finger) to draw blood, then applying the blood to a chemically active disposable 'test-strip'.Symmetry element: A symmetry element is a point of reference about which symmetry operations can take place. In particular, symmetry elements can be centers of inversion, axes of rotation and mirror planes.Sarcopenic obesity: Sarcopenic obesity is a medical condition which is actually a mix of two different ailments. It is a situation wherein a person shows an increase in fat mass and a reduction in lean mass.Glucose transporterList of U.S. states by life expectancy: This article presents a list of United States states sorted by their life expectancy at birth and by race/ethnicity in every state where the population of that racial or ethnic group is sufficiently large for robust estimates. The data is taken from the Measure of America's third national human development report, The Measure of America 2013–2014 width="25%" align="center" |Maladaptation: A maladaptation () is a trait that is (or has become) more harmful than helpful, in contrast with an adaptation, which is more helpful than harmful. All organisms, from bacteria to humans, display maladaptive and adaptive traits.Insulin-like growth factor 2: Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin. The MeSH definition reads: "A well-characterized neutral peptide believed to be secreted by the liver and to circulate in the blood.Alexander's law: Jacobson GP et al. Alexander's law revisited.TriglycerideLipotoxicity: Lipotoxicity is a metabolic syndrome that results from the accumulation of lipid intermediates in non-adipose tissue, leading to cellular dysfunction and death. The tissues normally affected include the kidneys, liver, heart and skeletal muscle.Indian Famine Codes: The Indian Famine Codes, developed by the colonial British in the 1880s, were one of the earliest famine scales. The Famine Codes defined three levels of food insecurity: near-scarcity, scarcity, and famine.Haplogroup L0 (mtDNA)Adenylate kinase: Adenylate kinase () (also known as ADK or myokinase) is a phosphotransferase enzyme that catalyzes the interconversion of adenine nucleotides, and plays an important role in cellular energy homeostasis.
(1/1289) The effect of dietary restriction during development in utero on the frequency of spontaneous somatic mutations.
Caloric or dietary restriction is known to be protective against cancer in humans and in mice but the mechanism is uncertain. Given that somatic mutations are important in carcinogenesis, dietary restriction may act by changing mutation rates. Indeed, previous studies have shown that reductions in caloric intake during development or in adult life make mice less susceptible to high doses of mutagens. In these studies there have been hints that the spontaneous mutant frequency may also be reduced, but no significant decrease has been observed save in one study of very old mice. Since the spontaneous mutant frequency is already low, reductions from this level require the use of much larger sample sizes than usual and larger than those used in the previous studies. As pre-existing mutations cannot be eliminated, it is necessary to reduce the dietary intake over a period of time when a substantial proportion of spontaneous mutations arise in order to see an effect. To overcome such problems, the dietary restriction in this study was applied during the time of the highest mutation rate, early development, and many more than the usual number of animals were studied. SWR female mice were crossed with Muta(TM)Mouse males to obtain F(1) progeny for analysis of mutant frequency. At conception, the dams were put into two groups, one that was fed ad libitum and another which was fed 80% of the ad libitum diet. Pups were killed at birth, DNA was extracted from the whole animal and used to measure the mutant frequencies of the mice at the cII locus. Although the weights of the pups from dams whose diet was restricted were significantly less than those of the ad libitum mice (P = 0.003), the litter sizes in the two groups were approximately the same and did not differ significantly (P = 0.13). There was no significant difference in the mutant frequencies in the dietarily restricted and ad libitum groups (P = 0.43). In addition, there was no significant correlation between the weights of the pups and their mutant frequency in either the ad libitum or dietarily restricted groups (r(2) = 0.14 and r(2) = 0.024). No difference was observed in mutant frequency between the ad libitum and dietarily restricted mice from litters of the same size (P = 0.61). These results indicate that the protective effect of dietary restriction on cancer rates is not mediated by an alteration in the spontaneous rate of mutation but rather by another mechanism, such as its effect on induced mutation. (+info)
(2/1289) Evidence that the decrease in liver glycogen is associated with the exercise-induced increase in IGFBP-1.
The purpose of the present study was to test the hypothesis that the exercise-induced increase in insulin-like growth factor binding protein (IGFBP)-1 is not always linked to a decrease in blood glucose level and to examine whether the decreasing levels of liver glycogen during exercise may be associated with the increase in IGFBP-1. Three groups of rats were submitted to a 70-min treadmill exercise. One group of rats was fed normally, and the two other groups had their food intake restricted by 50% (50% fast) the night before the experiment. One of these two 50% fasted groups of rats was infused (intravenously) with glucose throughout exercise to maintain euglycemia. Exercise in noninfused 50% fasted rats, compared with the normally fed rats, resulted in significantly lower blood glucose (minute 70) and insulin levels, significantly lower liver glycogen content, no change in IGF-I, and significantly higher increases in free fatty acid, glycerol, beta-hydroxybutyrate, and IGFBP-1. Maintenance of euglycemia during exercise in glucose-infused 50% fasted rats reduced to a large extent the decrease in insulin levels but only slightly attenuated the lipid response and the IGFBP-1 response seen in noninfused 50% fasted rats. Comparisons of all individual liver glycogen and IGFBP-1 values revealed that liver glycogen values were highly (P < 0.001) predictive of the IGFBP-1 response during exercise (R = 0.564). The present results indicate that the IGFBP-1 response during exercise is not always linked to a decrease in plasma glucose and suggest that the increase in IGFBP-1 during exercise may be related to the decrease in liver glycogen content. (+info)
(3/1289) Upregulated promitogenic signaling via cytokines and growth factors: potential mechanism of robust liver tissue repair in calorie-restricted rats upon toxic challenge.
Previously we reported that moderate calorie restriction or diet restriction (DR, calories reduced by 35% for 21 days) in male Sprague-Dawley rats protects from a lethal dose of thioacetamide (TA). DR rats had 70% survival compared with 10% in rats fed ad libitum (AL) because of timely and adequate compensatory liver cell division and tissue repair in the DR rats. Further investigation of the mechanisms indicate that enhanced promitogenic signaling plays a critical role in this stimulated tissue repair. Expression of stimulators of promitogenic signaling interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), hepatocyte growth factor (HGF), transforming growth factor-alpha (TGF-alpha), and epidermal growth factor receptor (EGFR) were studied during liver tissue repair after TA-induced liver injury. Plasma IL-6 was significantly higher in the DR rats, with 6-fold higher expression at 48 h after TA administration. Immunohistochemical localization revealed significantly higher expression of IL-6 in the hepatic sinusoidal endothelium of DR rats. Expression of TGF-alpha and HGF was consistently higher in the livers of DR rats from 36 to 72 h. EGFR, which serves as a receptor for TGF-alpha, was higher in DR rats before TA administration and remained higher till 48 h after TA intoxication. DR-induced 2-fold increase in hepatic iNOS activity is consistent with early cell division in DR rats after TA challenge. These data suggest that the reason behind the higher liver tissue repair after TA-induced hepatotoxicity in DR rats is timely and higher expression of the growth stimulatory cytokines and growth factors. It appears that the physiological effects of DR make the liver cells vigilant and prime the liver tissue promptly for liver regeneration through promitogenic signaling upon toxic challenge. (+info)
(4/1289) Chaperones come of age.
Chaperone function plays a key role in repairing proteotoxic damage, in the maintenance of cell architecture, and in cell survival. Here, we summarize our current knowledge about changes in chaperone expression and function in the aging process, as well as their involvement in longevity and cellular senescence. (+info)
(5/1289) High osmolarity extends life span in Saccharomyces cerevisiae by a mechanism related to calorie restriction.
Calorie restriction (CR) extends life span in many different organisms, including mammals. We describe here a novel pathway that extends the life span of Saccharomyces cerevisiae mother cells but does not involve a reduction in caloric content of the media, i.e., there is growth of yeast cells in the presence of a high concentration of external osmolytes. Like CR, this longevity-promoting response to high osmolarity requires SIR2, suggesting a common mechanism of life span regulation. Genetic and microarray analysis indicates that high osmolarity extends the life span by activating Hog1p, leading to an increase in the biosynthesis of glycerol from glycolytic intermediates. This metabolic shift likely increases NAD levels, thereby activating Sir2p and promoting longevity. (+info)
(6/1289) Effect of low protein and low energy diet on physiological status and digestibility of F344 rats.
A long-term raising study was carried out on male F344/DuCrj rats with three low protein (Crude Protein (CP); 14.5, 11.5, 8.5%) and low energy (Digestible Energy (DE); 2.0 kcal/g) diets from 4 to 104 weeks of age. In rats fed the 8.5% CP diet, body weight and digestible crude protein (DCP) consumption at 10 weeks of age were lower (P < 0.05) but the body weight at 50 weeks of age was higher (P < 0.05) than in the other groups. In rats fed the 8.5% CP diet the crude fat digestibility was higher (P < 0.05), and the CP/nitrogen-corrected metabolizable energy (MEn) ratio was low. On the other hand, the mean survival time at 80 weeks of age was shorter in rats fed the 8.5% CP diet (P < 0.05). (+info)
(7/1289) Differentiation between obesity and insulin resistance in the association with C-reactive protein.
BACKGROUND: Plasma C-reactive protein (CRP) concentrations are increased in obese and/or hyperinsulinemic individuals. The goal of this study was to determine if the relation between insulin resistance and CRP was independent of obesity. METHODS AND RESULTS: Plasma CRP concentrations were measured before and after 3 months of calorie restriction in 38 healthy, obese women. Steady-state plasma glucose (SSPG) concentration during a 180-minute infusion of octreotide, glucose, and insulin was used to stratify participants into insulin-resistant (IR, n=20) or insulin-sensitive (n=18) groups, similar in terms of mean age (46+/-2 versus 44+/-2 years), body mass index (32.0+/-0.4 versus 31.4+/-0.3 kg/m2), and waist circumference (96+/-2 versus 95+/-2 cm). Mean CRP (0.39+/-0.08 versus 0.12+/-0.03 mg/dL, P=0.003) concentrations were higher in the IR group, as were day-long plasma glucose and insulin responses (P<0.001). There was a significant correlation at baseline between CRP and day-long plasma integrated insulin response (r=0.47, P=0.001) but not between CRP and body mass index (r=0.14) or waist circumference (r=0.10). Weight loss was similar in the two groups (8.7+/-0.9 versus 8.4+/-0.8 kg) but was associated with significant (P<0.001) decreases in SSPG and CRP concentrations in the IR group only. Regression analysis showed that SSPG and day-long plasma insulin response were the only significant predictors of CRP concentration. CONCLUSIONS: CRP concentrations are elevated predominantly in obese individuals who are also insulin resistant and fall in parallel with weight loss-associated improvements in insulin resistance. The relation between CRP concentrations and insulin resistance is independent of obesity. (+info)
(8/1289) Lifelong caloric restriction increases expression of apoptosis repressor with a caspase recruitment domain (ARC) in the brain.
Aging may increase apoptotic events and the susceptibility of the central nervous system to apoptosis. Calorie restriction has been shown to have neuroprotective effects, but the mechanisms in vivo are unknown. We investigated apoptosis and apoptotic regulatory proteins in the brain frontal cortex of 12-month-old ad libitum fed, 26-month-old ad libitum fed, and 26-month-old calorie-restricted (CR) male Fischer 344 rats (CR = 40% restricted compared to ad libitum). We found that specific DNA fragmentation indicative of apoptosis was increased with age (+124%) in the cortices of the brain and that calorie restriction attenuated this increase significantly (-36%). We determined levels of ARC (apoptosis repressor with a caspase recruitment domain), which inhibits caspase-2 activity and also attenuates cytochrome c release from the mitochondria. We found a significant age-associated decline in ARC level, which was attenuated in the brains of the CR rats. In accordance with the changes in ARC expression observed, calorie restriction attenuated the increases in cytosolic cytochrome c and caspase-2 activity with age and suppressed the age-associated rise in cleaved caspase-9 and cleaved caspase-3. However, neither age nor calorie restriction had any effect on caspase-3 and caspase-9 activities. This data provides evidence for an increased incidence of apoptosis in rat brain with age and evidence that calorie restriction has the ability to attenuate this. Furthermore, our data suggest that calorie restriction provides neuroprotection through ARC by suppressing cytochrome c release and caspase-2 activity. (+info)