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 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 Materials: Materials fabricated by BIOMIMETICS techniques, i.e., based on natural processes found in biological systems.

The effect of dietary restriction during development in utero on the frequency of spontaneous somatic mutations. (1/1289)

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)

Evidence that the decrease in liver glycogen is associated with the exercise-induced increase in IGFBP-1. (2/1289)

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)

Upregulated promitogenic signaling via cytokines and growth factors: potential mechanism of robust liver tissue repair in calorie-restricted rats upon toxic challenge. (3/1289)

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)

Chaperones come of age. (4/1289)

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)

High osmolarity extends life span in Saccharomyces cerevisiae by a mechanism related to calorie restriction. (5/1289)

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)

Effect of low protein and low energy diet on physiological status and digestibility of F344 rats. (6/1289)

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)

Differentiation between obesity and insulin resistance in the association with C-reactive protein. (7/1289)

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)

Lifelong caloric restriction increases expression of apoptosis repressor with a caspase recruitment domain (ARC) in the brain. (8/1289)

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)

  • Therapeutic benefits of caloric restriction (CR) on clinical outcomes in the treatment of neurodegenerative disease, cancer, cardiovascular disease, and diabetes have been found. (
  • Even more pronounced effects were seen in 2.7-3.2-year-old mice exposed to 40% caloric restriction starting at 0.3 years of age. (
  • Over 11,000 genes were examined using high-density oligonucleotide microarrays in four groups of 10- to 11-month-old male C57Bl6 mice that were either fasted for 18 h before death (F), subjected to short-term caloric restriction for 23 days (SCR), or LCR for 9 months and compared with nonfasted control (CO) mice. (
  • The influence of caloric restriction on hepatic glyceraldehyde- and glycerol-metabolizing enzyme activities of young and old mice were studied. (
  • Aldehyde dehydrogenase and aldehyde reductase activities in both young and old CR mice were unchanged by caloric restriction. (
  • Materials and Methods: Caloric restriction (CR) was initiated in male mice at 14 wk of age at 10% restriction, increased to 25% restriction at 15 wk, and then increased to 40% restriction at 16 wk, where it was maintained until 24 wk of age when the study was terminated. (
  • Femur BMC, BMD, cortical thickness, and fracture strength decreased significantly in CR mice, but trabecular bone volume fraction in the femur did not change with food restriction. (
  • Down-regulation of intracellular nutrient signal pathways was proposed to be a primary mechanism of caloric restriction (CR)-mediated lifespan extension. (
  • Conclusions: Caloric restriction and its related weight reduction are associated with marked decreases in lean mass, fat mass, serum leptin and IGF-1, and cortical bone mass. (
  • Or if they were, they were losing much less than they thought they should be losing given the caloric reduction. (
  • It's one of the things that we're looking at in our lab, because if you know of a gene that mediates the affects of caloric restriction, then it may be a suitable target for drugs that have the same effects of caloric restriction but without you having to go on a diet - which most people don't want to do. (
  • Many simply don't believe this extreme diet is feasible, which is why some researchers focus on finding a pill that could mimic the effects of caloric restriction. (
  • The moderate caloric restriction did not reverse the changes promoted by the high-fat diet but induced a small decrease in adiposity, which was reversed after refeeding, and the animals maintained a dyslipidaemic profile and high fat deposition in the liver. (
  • We can conclude that the high-fat diet and subsequent moderate caloric restriction plus refeeding increased the risks of developing visceral obesity, dyslipidaemia and non-alcoholic fatty liver disease, which suggests that this type of experimental protocol can be used to study mechanisms related to the metabolic syndrome. (
  • Most surprisingly was that these positive effects of the liver were seen only three days after initiating the diet restriction. (
  • In rodents, caloric restriction reduces, and some fats increase, carcinogen-induced colon cancer incidence. (
  • Twenty-two to 30-year-old rhesus monkeys exposed to 30% caloric restriction since 7-14 years of age showed attenuation of age-related methylation drift compared to ad libitum-fed controls such that their blood methylation age appeared 7 years younger than their chronologic age. (
  • In some studies, caloric restriction has been shown to lower blood pressure, improve heart health and boost the immune system in people. (
  • In mammals, caloric restriction consistently results in extended lifespan. (
  • In an attempt to link these mechanisms to those typically associated with lifespan extension in the worm, Buck and colleagues demonstrated that treating worms with the antidepressant after caloric restriction failed to increase lifespan beyond that which occurred following caloric restriction alone. (
  • In addition, treatment with the drug had little effect on lifespan in worms expressing mutant proteins required to reap the benefits of caloric restriction. (
  • Evolutionary theory leads to the general expectation that dietary restriction will often result in increased survival probabilities, and thus increased lifespan. (
  • If this strong quantitative relationship were evolutionarily conserved among all mammals, then the prospects for a substantial increase in human lifespan from caloric restriction would be very good. (
  • Caloric restriction (CR) delays the onset of many age-related pathophysiological changes and extends lifespan. (
  • Attribution of the marginally longer Okinawan average lifespan to caloric restriction diets is silly: it's only a year or so longer than the Japanese lifespan, and less than 5 years longer than the US lifespan. (
  • 1,2 Two decades later, McCay et al first observed lifespan extension in laboratory rats maintained on a caloric restriction (CR) diet. (
  • We investigated the influences of short-term and lifespan-prolonging long-term caloric restriction (LCR) on gene expression in white adipose tissue (WAT). (
  • Only few years ago, researchers succeeded in prolonging the lifespan of worm C. elegans, fruit fly D. melongaster and rats by almost 50% through a simple caloric restriction - which immediately fueled hopes for having found one key to a longer life also for humans. (
  • Of course, we're very interested in other ways to mimic the signals of caloric restriction without the actual restriction, since in all the animals tested so far, caloric restriction results in serious extension of lifespan and youthspan. (
  • Caloric restriction (CR) has been shown in several-but not all-laboratory models to increase lifespan and to delay or slow the progression of a wide variety of aging changes and age-related pathologies. (
  • To date, caloric restriction (CR) is the most robust, non-genetic intervention able to increase lifespan and to reduce the rate of aging in several animal species. (
  • Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. (
  • 1 ], much interest has been shown in caloric restriction's ability to improve health and to extend lifespan. (
  • Caloric restriction can increase lifespan, reduce markers of physiological aging, and delay the onset of certain age-related diseases. (
  • The greater survival in the caloric restriction group confirms that the experimental treatment induced the lifespan enhancing effect. (
  • It is widely accepted that caloric restriction (CR) without malnutrition delays the onset of aging and extends lifespan in diverse animal models including yeast. (
  • Caloric restriction (CR) may retard aging processes and extend lifespan in organisms by altering energy-metabolic pathways. (
  • This effect of caloric restriction (CR) on lifespan has been reported in nearly all species tested and has been reproduced hundreds of times under a variety of different laboratory conditions. (
  • Caloric restriction (CR) and a reduced growth hormone (GH)-insulin-like growth factor (IGF-1) axis are associated with an extension of lifespan across taxa. (
  • It is widely held that caloric restriction (CR) extends lifespan by preventing or reducing the age-related accumulation of irreversible molecular damage. (
  • This system will be used to measure fly lifespan under caloric restriction analogous to current mammalian studies. (
  • Caloric restriction (CR) delays the onset of aging and extends lifespan in diverse experimental organisms through an unknown mechanism. (
  • The aging process is frequently affected by environmental factors, and caloric restriction is by far the most effective and established environmental manipulation for extending lifespan in various animal models. (
  • However, the precise mechanisms by which caloric restriction affects lifespan are still not clear. (
  • In this review, we assess the current advances in epigenetic regulation in response to caloric restriction and how this affects cellular senescence, aging and potential extension of a healthy lifespan in humans. (
  • Widely recognized methods of extending maximum lifespan in model organisms such as nematodes, fruit flies, and mice include caloric restriction, gene manipulation, and administration of pharmaceuticals. (
  • abstract = "Caloric restriction in animal models delays many age-related pathological conditions. (
  • One of the better supported results in the study of aging is that, for almost all species for which the experiment has been done-fruit flies are the exception-caloric restriction increases life expectancy. (
  • We propose that caloric restriction increases bioavailability of NO, decreases vascular reactive oxygen species generation, activates the Nrf2/antioxidant response element pathway, inducing reactive oxygen species detoxification systems, exerts antiinflammatory effects, and, thereby, suppresses initiation/progression of vascular disease that accompany aging. (
  • We conclude that intestinal permeability of medium size probes increases with aging and that lifelong caloric restriction does not prevent this change. (
  • Caloric restriction (CR), the consumption of fewer calories while avoiding malnutrition, decelerates the rate of aging and the development of age-related diseases. (
  • Caloric restriction (CR), the consumption of fewer calories while avoiding malnutrition, is a robust method of decelerating aging and the development of age-related diseases ( 1 ). (
  • Total caloric restriction (CR) without malnutrition is a well-established experimental approach to extend life span in laboratory animals. (
  • Twenty-two to 30-year-old rhesus monkeys exposed to 30% caloric restriction since 7-14 years of age showed attenuation of age-related methylation drift compared to ad libitum-fed controls such that their blood methylation age appeared 7 years younger than their chronologic age. (
  • When 25% caloric restriction was used for only the first 4 weeks after DMBA administration followed by ad libitum feeding, MT incidence was not affected. (
  • Caloric restriction and redox state: does this diet increase or decrease oxidant production? (
  • HealthDay News) - Implementation of a caloric restriction weight-loss diet, with or without exercise, is associated with measurable reductions in markers of inflammation for obese or overweight postmenopausal women. (
  • Recent studies of the treatment of obesity by moderate and severe caloric restriction show that patients treated in randomized trials using a conventional 1200 kcal/d reducing diet, combined with behavior modification, lose approximately 8.5 kg in 20 weeks. (
  • Overweight and obese postmenopausal women were randomized to 1-year: caloric restriction diet (goal of 10% weight loss, N = 118), aerobic exercise (225 min/wk of moderate-to-vigorous activity, N = 117), combined diet + exercise (N = 117), or control (N = 87). (
  • However, because participants in the established-plus-DASH treatment tended to lose more weight and reduce their waist circumference compared with participants in both the advice-only control condition and the JNC 6 established intervention condition, the incremental benefit of the DASH diet to lifestyle modifications of weight loss, exercise, and sodium restriction could not be determined. (
  • 11.7% caloric restriction was achieved, on average) or to maintain current diet (n=75) for two years. (
  • As it can be seen in figure 2, caloric restriction (CR), exercise (EX) and resveratrol (RSV) can induce AMPK and Sirtuin activities in different cells triggering mechanisms involved in mitochondrial homeostasis, oxidative respiration activation, mitochondrial biogenesis and auto/mitophagy. (
  • The title, ' Role of DNA methylation in the dietary restriction mediated cellular memory' suggests some underlying mechanisms have been uncovered which can explain the presumed healthful benefits of dietary restriction (DR). If so, then what exactly is the nature of these apparent relationships and what are their benefits? (
  • This prevented the worm from absorbing the nutrients that it would normally get from the food and so its body reacted as if it were undergoing caloric restriction. (
  • UT Southwestern Medical Center researchers find that an FDA-approved drug to treat high blood pressure seems to extend life span in worms via a cell signaling pathway that may mimic caloric. (
  • Mimic caloric restriction as a means to birth control? (
  • A recent paper published in GeroScience by researchers at the University of Oklahoma provides some much needed food for thought for the field of caloric restriction. (
  • Mild cellular stress that occurs with energy restriction is believed to produce a hormetic effect that leads to adaptive cell responses and resistance to disease. (
  • Graves JL (1993) The costs of reproduction and dietary restriction: parallels between insects and mammals. (
  • Caloric restriction (CR) retards several aspects of the aging process in mammals, including age-related mortality, tumorigenesis, physiological decline [ 1 ] and the establishment of age-related transcriptional profiles [ 2 ]. (