SEARCH · PubMed Health

Results for “Caloric Restriction”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

PubMed1996

Oxidative stress, caloric restriction, and aging.

Under normal physiological conditions, the use of oxygen by cells of aerobic organisms generates potentially deleterious reactive oxygen metabolites. A chronic state of oxidative stress exists in cells because of an imbalance between prooxidants and antioxidants. The amount of oxidative damage increases as an organism ages and is postulated to be a major causal factor of senescence. Support for this hypothesis includes the following observations: (i) Overexpression of antioxidative enzymes retards the age-related accrual of oxidative damage and extends the maximum life-span of transgenic Drosophila melanogaster. (ii) Variations in longevity among different species inversely correlate with the rates of mitochondrial generation of the superoxide anion radical (O2) and hydrogen peroxide. (iii) Restriction of caloric intake lowers steady-state levels of oxidative stress and damage, retards age-associated changes, and extends the maximum life-span in mammals.

Aging↗

PubMed2001

Effect of short-term caloric restriction on H2O2 production and oxidative DNA damage in rat liver mitochondria and location of the free radical source.

Oxygen free radicals (ROS) of mitochondrial origin seem to be involved in aging. Whereas in other tissues complexes I or III of the respiratory chain contain the ROS generators, in this study we find that rat liver mitochondria generate oxygen radicals at complexes I, II, and III. Short-term (6 weeks) caloric restriction significantly decreased H2O2 production in rat liver mitochondria. This decrease in ROS production was located at complex I because it occurred with complex I-linked substrates (pyruvate/malate), but did not reach statistical significance with the complex II-linked substrate succinate. The mechanism responsible for the lowered ROS production was not a decrease in oxygen consumption. Instead, the mitochondria of caloric-restricted animals released less ROS per unit electron flow. This was due to a decrease in the degree of reduction of the complex I generator. Furthermore, oxidative damage to mitochondrial and nuclear DNA was also decreased in the liver by short-term caloric restriction. The results agree with the idea that caloric restriction delays aging, at least in part, by decreasing the rate of mitochondrial ROS generation and thus the rate of attack to molecules, like DNA, highly relevant for the accumulation of age-dependent changes.

Animals↗

PubMed2006

One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue.

BACKGROUND: Caloric restriction (CR) increases maximal life span in short-lived organisms, and its effects are being explored in nonhuman primates. The objectives of this study were to determine the feasibility of prolonged CR in nonobese adults and to compare the effects of CR- and exercise-induced weight loss on body composition and abdominal adiposity. METHODS: A randomized, controlled trial was conducted with 48 healthy, nonobese women and men, aged 57 +/- 1 (mean +/- standard error [SE]) years, with body mass index 27.3 +/- 0.3 kg/m2. Participants were randomly assigned to a 20% calorically-restricted diet (CR, n = 19), exercise designed to produce a similar energy deficit (EX, n = 19), or a healthy lifestyle control group (HL, n = 10) for 1 year. Assessments included weight, body composition by dual-energy x-ray absorptiometry, abdominal adipose tissue by magnetic resonance imaging, and energy intake by doubly labeled water. RESULTS: The average level of CR achieved by the CR group was 11.5 +/- 2.1%, and the EX group completed 59 +/- 6.7% of their prescribed exercise. Weight changes were greater (p <or=.0005) in the CR (-8.0 +/- 0.9 kg) and EX (-6.4 +/- 0.9) groups as compared to the HL group (-1.3 +/- 0.9 kg), corresponding to reductions of 10.7%, 8.4%, and 1.7% of baseline weights, respectively. Whole-body fat mass and visceral and subcutaneous abdominal adipose tissue decreased significantly (p <.005) and comparably in the CR and EX groups, but did not change in the HL group. CONCLUSIONS: CR for 1 year was feasible, but the level of CR achieved was less than prescribed. CR and exercise were equally effective in reducing weight and adiposity.

Abdominal Fat↗

PubMed2005

Three weeks of caloric restriction alters protein metabolism in normal-weight, young men.

The effects of prolonged caloric restriction (CR) on protein kinetics in lean subjects has not been investigated previously. The purpose of this study was to test the hypotheses that 21 days of CR in lean subjects would 1) result in significant losses of lean mass despite a suppression in leucine turnover and oxidation and 2) negatively impact exercise performance. Nine young, normal-weight men [23 +/- 5 y, 78.6 +/- 5.7 kg, peak oxygen consumption (Vo2 peak) 45.2 +/- 7.3 ml.kg(-1).min(-1), mean +/- SD] were underfed by 40% of the calories required to maintain body weight for 21 days and lost 3.8 +/- 0.3 kg body wt and 2.0 +/- 0.4 kg lean mass. Protein intake was kept at 1.2 g.kg(-1).day(-1). Leucine kinetics were measured using alpha-ketoisocaproic acid reciprocal pool model in the postabsorptive state during rest and 50 min of exercise (EX) at 50% of Vo2 peak). Body composition, basal metabolic rate (BMR), and exercise performance were measured throughout the intervention. At rest, leucine flux (approximately 131 micromol.kg(-1).h(-1)) and oxidation (R(ox); approximately 19 micromol.kg(-1).h(-1)) did not differ pre- and post-CR. During EX, leucine flux (129 +/- 6 vs. 121 +/- 6) and R(ox) (54 +/- 6 vs. 46 +/- 8) were lower after CR than they were pre-CR. Nitrogen balance was negative throughout the intervention ( approximately 3.0 g N/day), and BMR declined from 1,898 +/- 262 to 1,670 +/- 203 kcal/day. Aerobic performance (Vo2 peak, endurance cycling) was not impacted by CR, but arm flexion endurance decreased by 20%. In conclusion, 3 wk of caloric restriction reduced leucine flux and R(ox) during exercise in normal-weight young men. However, despite negative nitrogen balance and loss of lean mass, whole body exercise performance was well maintained in response to CR.

Adolescent↗

PubMedDate not supplied

Effect of age and caloric restriction on insulin receptor binding and glucose transporter levels in aging rats.

We report on the effect of age and chronic caloric restriction (CR) on insulin binding and glucose transporter content in both diaphragm and heart muscle membrane of young (11 months), mid-age (17 months), and old (29 month) ad libitum fed and CR Brown-Norway rats. The control animals received rat chow ad lib and CR animals were allowed 60% of ad libitum food. The CR regimen was initiated at four months of age and the animals were maintained on their respective diets until necropsy. There was no effect of age on insulin binding for either ad libitum or CR animals at each age evaluated. Caloric restriction significantly lowered insulin levels at each age studied when compared to the ad libitum-fed rats. However, CR animals were noted to have increased insulin binding (p < 0.001) compared to ad libitum-fed animals at each age for diaphragm muscle. For the heart, there appeared to be a decreased binding, particularly at higher insulin concentrations, in CR-fed animals. There was no net change in Glut-1 or Glut-4 levels for heart muscle membrane, or Glut-4 levels for diaphragm muscle membrane between ad libitum or CR animals. This data indicates that caloric restriction may have tissue-specific effects for insulin receptor binding, and that the improved insulin sensitivity in CR states is not a result of altered glucose transporter protein content.

Aging↗

PubMedDate not supplied

Effect of caloric restriction on age-associated cancers.

Caloric restriction (CR) without malnutrition in mice and rats reduces the incidence of spontaneous tumors and delays their appearance while increasing maximum life span. These results depend largely on CR per se, and not on low intakes of fat or other nutrients. Although most studies have tested CR imposed early in life, CR started in midadulthood also retards cancer and aging. The way(s) by which CR impedes cancers remain unclear, but possibilities include less cellular oxidative damage, retarded immunologic aging, hormonal changes, less energy available for cell proliferation, reduced exposure to dietary carcinogens and promoters, enhanced DNA repair, and less carcinogen activation. Far less is known about the relationship between caloric intake and cancer incidence in humans; however, recent findings suggest a positive association for certain cancers.

Aging↗

PubMed1999

Cellular proliferation potential during aging and caloric restriction in rhesus monkeys (Macaca mulatta).

Caloric restriction (CR) is the most successful method of extending both median and maximal lifespans in rodents and other short-lived species. It is not yet clear whether this method of life extension will be successful in longer-lived species, possibly including humans; however, trials in rhesus monkeys are underway. We have examined the cellular proliferative potential of cells from CR and AL (ad libitum fed) monkey skin cells using two different bioassays: colony size analysis (CSA) of dermal fibroblasts isolated and cloned directly from the skin and beta-galactosidase staining at pH 6.0 (BG-6.0) of epidermal cells in frozen sections of skin. Decreases in both proliferative markers occurred with age, but no differences were observed between CR and AL animals. Skin biopsies were obtained from AL and CR rhesus monkeys from two different aging colonies, one at the National Institute on Aging (NIA) and one at the University of Maryland-Baltimore (UMB). These biopsies were used as a source of tissue sections and cells for two biomarkers of aging assays. The CR monkeys had been maintained for 9-12 years on approximately 70% of the caloric intake of control AL animals. In the CSA studies, the fraction of small clones increased significantly and the fraction of large clones decreased significantly with increasing age in AL monkeys. The frequency of epidermal BG-6.0 staining cells increased with age in older (>22 years) AL monkeys, but most predominately in those of the UMB colony, which were somewhat heavier than the NIH AL controls. Old monkeys on CR tended to have fewer BG-6.0-positive cells relative to old AL-derived epidermis, but this effect was not significant. These results indicate that cellular proliferative potential declined with age in Macaca mulatta, but was not significantly altered by CR under these conditions. Although these experiments are consistent with an absence of effect of CR on monkey skin cell proliferative potential, we have found in previous experiments with mice that a longer duration of CR (as a fraction of total lifespan) was needed to demonstrate CR-related improvement in clone size in mice. Further studies on the now mid-aged monkeys will be needed as their age exceeds 20 years to conclusively rule out an effect of CR on proliferative potential of skin cells from these primates.

Aging↗

PubMed1996

Life-long moderate caloric restriction prolongs reproductive life span in rats without interrupting estrous cyclicity: effects on the gonadotropin-releasing hormone/luteinizing hormone axis.

Restricting food intake to 60% that of ad libitum-fed rats results in an extended life span, reduced incidence of age-related diseases, and delayed reproductive senescence. We used this animal model to further elucidate the mechanisms whereby reproductive senescence is delayed. Female Sprague-Dawley rats (7 wk old) were calorically restricted (CR; n = 70) to 60% of the ad libitum(AL) intake measured in control rats (n = 70). Rats were individually housed under a 14L:10D cycle and fed daily within 1.5 h of lights-off. Body weights were monitored every 2 wk, and vaginal lavage was performed until rats were ovariectomized (OVX). Two weeks after OVX, when rats were 4, 12, or 18 mo of age, blood samples were taken via jugular cannulae every 6 min for 3 h, and the plasma was assayed for rat LH. The resulting profiles were examined through use of Cluster analysis for mean LH concentrations, LH pulse amplitude, and interval between LH pulses. CR rats grew at a slower rate, and then maintained body weights at approximately 76% that of AL controls between 4 and 17.5 mo of age. The onset of persistent estrus was delayed by 4 mo in CR rats. Average cycle length was longer (p < 0.01) by less than 0.5 days in CR compared with AL rats between 3.5 and 5.5 mo of age but not different between 6.5 and 11.5 mo. Mean levels of LH in OVX rats decreased with age (p < 0.01), increased with caloric restriction (p < 0.05), and decreased with declining cycling status of the animal prior to OVX (regular [reg] vs. irregular [ir] vs. persistent estrus [pe]; p < 0.05). The increased mean LH due to caloric restriction was attributed to an increase in mean pulse amplitude and not to a decrease in time interval between LH pulses. From these data we conclude that the beneficial effects of caloric restriction on reproductive longevity may be acting at the level of the hypothalamus and/or pituitary to enhance LH secretion and do not require a delay in puberty or a period of acyclicity.

Aging↗

PubMed2003

Are mice calorically restricted in nature?

An important question about traditional caloric restriction (CR) experiments on laboratory mice is how food intake in the laboratory compares with that of wild mice in nature. Such knowledge would allow us to distinguish between two opposing views of the anti-aging effect of CR--whether CR represents, in laboratory animals, a return to a more normal level of food intake, compared with excess food consumption typical of laboratory conditions or whether CR represents restriction below that of animals living in nature, i.e. the conditions under which house mice evolved. To address this issue, we compared energy use of three mouse genotypes: (1) laboratory-selected mouse strains (= laboratory mice), (2) house mice that were four generations or fewer removed from the wild (= wild-derived mice) and (3) mice living in nature (= wild mice). We found, after correcting for body mass, that ad libitum fed laboratory mice eat no more than wild mice. In fact, under demanding natural conditions, wild mice eat even more than ad libitum fed laboratory mice. Laboratory mice do, however, eat more than wild-derived mice housed in similar captive conditions. Therefore, laboratory mice have been selected during the course of domestication for increased food intake compared with captive wild mice, but they are not particularly gluttonous compared with wild mice in nature. We conclude that CR experiments do in fact restrict energy consumption beyond that typically experienced by mice in nature. Therefore, the retarded aging observed with CR is not due to eliminating the detrimental effects of overeating.

Age Factors↗

PubMed2004

Peripheral lymphocyte 8-OHdG levels correlate with age-associated increase of tissue oxidative DNA damage in Sprague-Dawley rats. Protective effects of caloric restriction.

8-hydroxy-deoxyguanosine adducts (8-OHdG), indices of oxidative DNA damage, were measured by immunohystochemistry with diaminobenzidine detection in the brain, skeletal muscle, heart, liver, tenuum mucosa and lymphocytes from young (4 months) and aged (24 months) Sprague-Dawley rats fed ad libitum or held on two different caloric restriction diets (alternate day ad libitum feeding or daily feeding with 40% reduced calories). In the absence of caloric restriction the levels of oxidative DNA damage increased as a function of age in all tissues examined, with a maximum approximately 3-fold increase being detected in the peripheral lymphocytes and the heart and a minimum approximately 2-fold increase being detected in the liver and brain tissues. Caloric restriction regimens effectively reduced age-dependent increase of oxidative DNA damage in all tissues examined; in particular, the brain and small intestine did not exhibit any age-related increase of oxidative DNA damage. We propose that the levels of 8-OHdG in peripheral lymphocytes may serve a biochemical index of age-related whole organism oxidative DNA damage. Immunohistochemistry might be exploited as a rapid and simple techniques for measuring lymphocytes oxidative DNA damage in large scale studies.

8-Hydroxy-2'-Deoxyguanosine↗

PubMedDate not supplied

The retardation of aging by caloric restriction: studies in rodents and primates.

Caloric restriction (CR), which has been investigated by gerontologists for more than 60 yr, provides the only intervention tested to date in mammals (typically mice and rats) that repeatedly and strongly increases maximum life span while retarding the appearance of age-associated pathologic and biologic changes. Although the large majority of rodent studies have initiated CR early in life (1-3 mo of age), CR started in midadulthood (at 12 mo) also extends maximum life span in mice. Two main questions now face gerontologists investigating CR. By what mechanisms does CR retard aging and disease processes in rodents? There is evidence to suggest that age-associated increases in oxidative damage may represent a primary aging process that is attenuated by CR. Will CR exert similar actions in primates? Studies in rhesus monkeys subjected to CR and limited human epidemiological data support the notion of human translatability. However, no matter what the answers are to these questions, the prolongation of the health span and life span of rodents by CR has major implications for many disciplines, including toxicologic pathology, and raises important questions about the desirability of ad libitum feeding.

Aging↗

PubMed2001

Leptin and anti-aging action of caloric restriction.

Evolutional theories of aging and caloric restriction (CR) in animals predict the presence of neuroendocrine signals to divert the limited energy resources from energy-costly physiologic processes such as reproduction to those essential for survival in response to food shortage. The diversion of energy and subsequent molecular mechanisms might extend the lifespan. A growing body of evidence indicates that leptin, a peptide hormone secreted from adipocytes, has a key role in neuroendocrine adaptation against life-threatening stress such as fasting. The present review discusses the potential role of leptin in the anti-aging action of CR. Although several alternative signaling pathways might also mediate the anti-aging action of CR, leptin signaling could be a substantial pathway in the CR action. Research on neuroendocrine mechanisms of CR is warranted, because such efforts might provide clues to the regulation of the aging process in humans.

Aging↗

PubMed2003

Adipose tissue energy metabolism: altered gene expression profile of mice subjected to long-term caloric restriction.

We investigated the influences of short-term and lifespan-prolonging long-term caloric restriction (LCR) on gene expression in white adipose tissue (WAT). 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. Only a few transcripts of F and SCR were differentially expressed compared with CO mice. In contrast, 345 transcripts of 6,266 genes found to be expressed in WAT were altered significantly by LCR. The expression of several genes encoding proteins involved in energy metabolism was increased by LCR. Further, many of the shifts in gene expression after LCR are known to occur during adipocyte differentiation. Selected LCR-associated alterations of gene expression were supported by quantitative reverse transcriptase-polymerase chain reaction, histology, and histochemical examinations. Our data provide new insights on the metabolic state associated with aging retardation by LCR.

Adipose Tissue↗

PubMed1993

Long-term caloric restriction improves baroreflex sensitivity in aging Fischer 344 rats.

The effects of aging and caloric restriction on mean arterial pressure (MAP), heart rate (HR), and baroreflex sensitivity were determined in young (7-9 months) and old (22-24 months) awake, male Fischer 344 rats which had been either ad libitum fed or calorie restricted (60% of the ad libitum calories). The MAP of young rats was higher than that of old rats. The MAP of old ad libitum fed rats was higher than that of old restricted rats with no effect of diet in young rats. The HR of restricted rats was lower than ad libitum fed rats with no significant age effect. Reflex bradycardia to hypertensive episodes was greater in restricted than in ad libitum fed rats. Reflex tachycardia to hypotensive episodes was greater in young than in old rats and greater in calorie restricted than in ad libitum fed rats. These findings demonstrate that caloric restriction alters the age-associated decline in several hemodynamic parameters.

Aging↗

PubMed2002

Anti-aging effects of caloric restriction: Involvement of neuroendocrine adaptation by peripheral signaling.

Many hormonal signals from peripheral tissues contribute to the regulation of energy homeostasis and food intake. These regulators including leptin, insulin, and ghrelin, modulate the orexigenic and anorexigenic neuropeptide expression in hypothalamic nuclei. The anti-aging effects of caloric restriction have been explained from an evolutional viewpoint of the adaptive response of the neuroendocrine and metabolic response systems to maximize survival during periods of food shortage. In organisms, excess energy is stored in adipose tissues as a triglyceride preparation for such survival situations. Adipose tissue has recently been recognized as an endocrine organ, and leptin, as secreted by adipocyte, seems to be an especially important factor for the adaptive response to fasting and neuroendocrine alterations under caloric restriction. In this review, we discuss the potential involvement of neuroendocrine modulators in longevity and the anti-aging effects of caloric restriction.

Adaptation, Physiological↗

PubMed2006

Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates.

Caloric restriction (CR) has long been known to increase median and maximal lifespans and to decreases mortality and morbidity in short-lived animal models, likely by altering fundamental biological processes that regulate aging and longevity. In rodents, CR was reported to delay the aging of the immune system (immune senescence), which is believed to be largely responsible for a dramatic increase in age-related susceptibility to infectious diseases. However, it is unclear whether CR can exert similar effects in long-lived organisms. Previous studies involving 2- to 4-year CR treatment of long-lived primates failed to find a CR effect or reported effects on the immune system opposite to those seen in CR-treated rodents. Here we show that long-term CR delays the adverse effects of aging on nonhuman primate T cells. CR effected a marked improvement in the maintenance and/or production of naïve T cells and the consequent preservation of T cell receptor repertoire diversity. Furthermore, CR also improved T cell function and reduced production of inflammatory cytokines by memory T cells. Our results provide evidence that CR can delay immune senescence in nonhuman primates, potentially contributing to an extended lifespan by reducing susceptibility to infectious disease.

Age Factors↗

PubMed2004

Long-lived growth hormone receptor knockout mice: interaction of reduced insulin-like growth factor i/insulin signaling and caloric restriction.

Reduced IGF-I/insulin signaling and caloric restriction (CR) are known to extend the life span and delay age-related diseases. To address the interaction of these two interventions, we subjected normal (N) and long-lived GH receptor knockout (GHRKO) mice to CR for 20 months starting at weaning. We also used bovine GH transgenic (bGH Tg) mice, which overexpress GH and are short-lived and insulin resistant, for comparison. Circulating insulin and IGF-I levels were reduced by CR in N animals, whereas GHRKO animals exhibited very low insulin and undetectable IGF-I. Consistently, hepatic Akt phosphorylation was reduced by CR and was very low in GHRKO mice. bGH Tg mice exhibited increased active Akt. The forkhead box O1 (Foxo1) transcription factor was additively increased by CR and GHRKO at the mRNA level. However, Foxo1 protein levels were only elevated in GHRKO mice. The coactivator peroxisome proliferator-activated receptor-gamma coactivator 1alpha was increased at both gene and protein levels in GHRKO mice. N-CR and GHRKO mice also exhibited increased phosphorylated cAMP response element-binding protein and active p38 compared with the N ad libitum-fed mice, and the levels of these proteins were greatly diminished in bGH Tg mice. The protein levels of the deacetylase sirtuin 1 (SIRT1) were elevated in the two CR groups and, unexpectedly, also in bGH Tg mice. These results suggest a major role for the Akt/Foxo1 pathway in the regulation of longevity in rodents. An activated gluconeogenic pathway and increased fat metabolism may be involved in mediating the effects of reduced somatotropic and insulin signaling on longevity. These results also add to the evidence that targeted disruption of the GH receptor/GH-binding protein gene and CR act via overlapping, but distinct, mechanisms.

Adenylate Kinase↗

PubMed1992

Skin fibroblasts from aged Fischer 344 rats undergo similar changes in replicative life span but not immortalization with caloric restriction of donors.

We have compared the in vitro replicative life span and characteristics of immortalization of skin fibroblast cultures derived from ad libitum-fed and caloric-restricted Fischer 344 rats of 6, 24, and 29 months of age. Cells from all 6-, 24-, and 29-month-old animals showed a gradual decline in proliferative potential as evidenced by decreases in harvest density, in the fraction of cells initiating DNA synthesis, and in the number of population doublings per passage. These declines were accompanied by morphological changes including cell enlargement. The replicative life span prior to immortalization decreased significantly with donor age (P less than 0.0001), while caloric restriction had no effect on the cumulative population doubling level. Prior to immortalization mitotic cells from all cultures showed a normal rat karyotype. Postcrisis cultures tended to have more polyploid cells but there were no characteristic or specific chromosomal changes found in the cells with an immortalized phenotype. Interestingly, fibroblasts derived from caloric-restricted animals had a significantly slower growth rate through the tenth week after immortalization (P less than 0.005). When these cultures were seeded at one-quarter the normal seeding density, to favor the outgrowth of the fastest growing cells, a population with a more "transformed" phenotype emerged.

Age Factors↗