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Results for “Caloric Restriction”

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At least 19 recordsLinked to original sources

PubMed2001

Altered leptin signaling is sufficient, but not required, for hypotension associated with caloric restriction.

Caloric restriction of mammals leads to decreases in blood pressure and heart rate. Although relevant clinically, the mechanisms involved, in terms of hormones and signaling pathways invoked, are currently not known. Circumstantial evidence suggests that leptin signaling may be involved with the bradycardia and hypotension associated with caloric restriction. This hypothesis was specifically tested using leptin-deficient mice (ob/ob) or leptin-receptor rats (Koletsky). Ob/ob mice were hypertensive during the light cycle relative to littermate controls (108 +/- 2 vs. 100 +/- 2 mmHg, respectively). Both ob/ob mice and wild-type mice exhibited hypotension and bradycardia on initiation of a 50% caloric restriction regime, suggesting that the loss of leptin during caloric restriction is not required to explain the cardiovascular effects. Blood pressure in Koletsky rats did not drop in response to caloric restriction during the light cycle, whereas blood pressure in littermate control rats significantly dropped. These data suggest that at least two pathways are involved with cardiovascular effects of caloric restriction: one dependent on leptin signaling and the other independent of the leptin axis.

Animals↗

PubMed1987

Biochemical alterations in 7,12-dimethylbenz[a]anthracene-induced mammary tumors from rats subjected to caloric restriction.

Caloric restriction reduces the incidence and progression of a broad spectrum of neoplastic diseases, yet little is known about the biochemical and molecular mechanisms involved. Profiles of enzyme activities of importance in cellular energy utilization were examined in 7,12-dimethylbenz[a]anthracene-induced (DMBA) mammary adenocarcinomas from rats fed ad libitum or calorically restricted diets. The diets provided equal nutrients except for fewer carbohydrate-derived calories; graded caloric restriction was 10, 20, 30 and 40%. The specific activities of hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, malic enzyme and fructose-1,6-bisphosphatase were all elevated to varying degrees in both large palpable and small, non-palpable tumors from calorically restricted hosts compared to activities in tumors from ad libitum-fed rats. Phosphofructokinase activity was increased in palpable tumors from calorically restricted hosts but markedly reduced in non-palpable tumors. These results suggest adaptive or compensatory alterations in tumor enzyme profiles in response to the altered nutritional state of the host.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1997

The age-associated alterations in late diastolic function in mice are improved by caloric restriction.

Caloric restriction reduces the magnitude of many age-related changes in rodents. Cardiac function is altered with senescence in mice, rats, and healthy humans. We examined the effects of life-long caloric restriction on diastolic and systolic cardiac function in situ using Doppler techniques in ad libitum-fed 30- to 32-month-old (AL) and calorically restricted (CR) 32- to 35-month-old female B6D2-F1 hybrid mice. The heart weight to body weight ratio was similar in AL (5.74 +/- .24 mg/g) and CR (5.68 +/- .20 mg/g) mice. Two systolic functional parameters known to decrease with age in both humans and mice, peak aortic velocity and aortic acceleration, were unchanged by CR compared to AL. In contrast, diastolic function was altered by caloric restriction. Although left ventricular peak early filling velocity (E) was not different between CR and AL, peak atrial filling velocity (A) was 50% lower in CR compared to AL (p < .001). The ratio of early diastolic filling to atrial filling (E/A ratio) was 64% higher in the CR (2.74 +/- .31) than the AL (1.55 +/- .07; p = .004). The fraction of ventricular filling due to atrial systole, the atrial filling fraction, was also reduced in CR (.21 +/- .04) compared to AL (.36 +/- .02; p = .007). These changes occurred in CR without alteration in E deceleration time, which is consistent with improved diastolic function in CR. Through mechanisms that remain unknown, lifelong caloric restriction may prevent the age-related impairments in late diastolic function but does not alter the impairments in systolic or early diastolic cardiac function.

Aging↗

PubMed1989

Growth factor binding to 7,12-dimethylbenz(a)anthracene-induced mammary tumors from rats subject to chronic caloric restriction.

Caloric restriction (CR) inhibits tumorigenesis in rodents. To understand the basis for this effect the binding of insulin, insulin-like growth factor I/somatomedin C (IGF-I/Sm-C), insulin-like growth factor II/multiplication stimulating activity (IGF-II/MSA), and epidermal growth factor were examined to membrane preparations of 7,12-dimethylbenz(a)anthracene-induced mammary adenocarcinomas and several normal tissues from female Sprague-Dawley rats. Animals were fed ad libitum (AL) or 25% and 40% calorically restricted diets. Large, palpable (LP) and small, less than or equal to 100 mg, nonpalpable (SNP) tumors were evaluated. Growth factor binding to tumors was differentially affected by CR. IGF-I/Sm-C binding was comparable for AL-LP, AL-SNP, and 25% CR-LP tumors, but elevated in 25% CR-SNP tumors. Scatchard analysis revealed high and low affinity IGF-I/Sm-C binding sites, with AL-SNP and 25% CR-SNP tumors exhibiting similar levels of high affinity sites and at a greater concentration than AL-LP and 25% CR-LP tumors. Insulin binding to mammary tumors was low, i.e., 8- to 13-fold lower than IGF-I/Sm-C binding. The 25% CR-LP and SNP tumors bound 2- to 5-fold more insulin than corresponding AL-LP and SNP tumors. Binding of IGF-II/MSA to these tumor preparations was high, approximately 11- to 25-fold greater than insulin binding, and was unaffected by CR or tumor size. The binding of epidermal growth factor was not detected in any tumor preparations. Receptor binding studies were confirmed with covalent cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses. Normal tissues exhibited tissue- and growth factor-specific alterations in binding with host CR. Thus, alterations in growth factor binding were not tumor specific, but were less pronounced than in mammary tumors. These findings suggest alterations in IGF-I/Sm-C and insulin binding properties to tumors in relation to CR and tumor size may contribute, in part, to the inhibitory effects of CR on tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2002

Cytokine responses in young and old rhesus monkeys: effect of caloric restriction.

Caloric restriction (CR) is the only known intervention demonstrated to retard a great variety of aging processes, extend median and maximum life-span, and decrease the incidence of age-associated diseases in mammals. Paralleling findings from rodent studies, studies in rhesus monkeys (Macaca mulatta) suggest that CR may retard many age-sensitive parameters in primates. A recent study in rhesus monkeys showed age-related dysregulation of cytokine levels. Specifically, age-related increases in interleukin-10 (IL-10) and IL-6 proteins were observed in supernatants from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs), and interferon-gamma (IFN-gamma) protein exhibited an age-related decrease in phytohemagglutinin (PHA)-stimulated PBMCs. To investigate effects of CR on age-related changes in cytokine production, we obtained PBMCs from control and CR rhesus monkeys aged 6-7 and 22-25 years. We evaluated IL-10 and IL-6 protein and gene expression after exposure to LPS and IFN-gamma protein and gene expression after PHA stimulation. The results revealed significantly higher levels of IFN-gamma protein and gene expression in aged monkeys on CR for 2 years compared with controls. No significant CR effects were observed on IL-10 and IL-6 protein levels. IFN-gamma plays an important role in the initial defense mechanism against viral and microbial disease and cancer. Altered regulation of IFN-gamma in old CR rhesus monkeys may be a key factor in reducing cancer incidence and other age-associated diseases.

Aging↗

PubMed2000

In vitro oxidation of low-density lipoprotein in two species of nonhuman primates subjected to caloric restriction.

Caloric restriction (CR), which increases longevity and retards age-associated diseases in laboratory rodents, is being evaluated in nonhuman primate trials. CR reduces oxidative stress in rodents and appears to improve risk factors for cardiovascular disease in nonhuman primates. We tested the hypothesis that low-density lipoprotein (LDL) oxidizability is reduced in two monkey species (rhesus and cynomolgus) subjected to chronic CR. In both species, no significant differences occurred between CR and control animals on total, LDL, or high-density lipoprotein (HDL) cholesterol. In rhesus monkeys, triglycerides were higher in controls than CR (139 +/- 23 vs 66 +/- 8 mg/dl,p < .01, respectively). LDL from CR rhesus monkeys was reduced in triglyceride content and molecular weight compared to controls, whereas LDL composition in cynomolgus monkeys was similar in CR and control animals. In keeping with minor deviations in lipids, antioxidants, and LDL composition, no consistent differences in in vitro LDL oxidizability were apparent between CR and controls in either species.

Animals↗

PubMed1987

Iatrogenic caloric restriction in pregnancy and birthweight.

The effects on fetal growth of iatrogenic prescription for dietary restriction in pregnancy have been infrequently assessed, and results have suggested large decrements in birthweight. We therefore related maternal dietary restriction to fetal growth among participants in the National Collaborative Perinatal Project at the Columbia Presbyterian Medical Center in New York. There were 255 women who delivered term infants with birthweights under the 31st percentile (low birthweight), who were each matched to women who delivered heavier term infants, within ethnic and gestational age strata. On review of antenatal records, 198 women were identified who had received a physician's recommendation to restrict caloric intake to 1800 kcal/day or below. The odds ratio between caloric restriction and low birthweight was 0.88 (not significant [NS]). Rates of maternal weight gain were controlled by linear multiple regression analysis, since higher weight gain was associated both with the likelihood of having a diet prescribed and with higher birthweight. With control for weight gain, although the odds ratio was reversed, the change was of small magnitude and not statistically significant. We found no relationship between medical advice to limit caloric intake during pregnancy and intrauterine growth retardation. Since women asked to limit caloric intake continued to gain more weight than others, the results are consistent with lack of compliance with the dietary regimen.

Adult↗

PubMed1995

Is late-life caloric restriction beneficial?

Caloric restriction initiated in young mice and rats results in increases in mean and median life span. When caloric restriction is implemented in older animals, an increase in life span is still observed; however, the magnitude of the increase is not as great as that observed in animals calorie restricted since they were young. Here we report the results of a pilot study in which caloric restriction was initiated in mature, older rats. Survival rates and terminal pathology were characterized and compared between a cohort of 17 continually ad libitum fed Long Evans rats and a cohort of 18 Long Evans rats, which were gradually introduced to 33% restriction in diet consumption at 18 months of age. No difference in the median life span was observed between the two groups. The data suggest there may be a level of maturity, or a stage in the aging process, after which caloric restriction no longer increases longevity.

Aging↗

PubMed1993

Protein restriction (PR) and caloric restriction (CR) compared: effects on DNA damage, carcinogenesis, and oxidative damage.

Protein restriction (PR) and caloric restriction (CR) similarly impinge upon various physiological factors that can significantly inhibit the growth of DNA-damaged tissue and, therefore, carcinogenesis. Whether this effect is largely, or only in part, due to simple inhibition of body weight gain is examined. Among their many other health-improving effects, PR and CR delay the onset of puberty. It has been suggested that animals have developed mechanisms to cope with lean periods and that, when food is limited, resources are diverted from those physiological functions that offer no benefit for immediate survival (e.g., reproductive capacity) to thereby support an increase in the maintenance functions that prolong life. PR has also been shown to affect numerous other varied mechanisms that can affect carcinogenesis, including gene expression and metabolism of xenobiotics. The effects of PR on initiational and promotional growth of DNA-damaged tissue is also discussed. PR also seems to boost antioxidant defenses and inhibit the accumulation of oxidative damage (as does CR). Protein restricted animals have been shown to accumulate more calories, but develop fewer preneoplastic lesions and tumors than their high-protein counterparts. This observation seems quite counter to most ideas about dietary restrictions and CR. Despite the fact that both PR and CR induce many beneficial physiological effects in common, it is possible that PR is the more feasible option for human consideration. The levels of PR likely to improve health without negative side effects are discussed.

Animals↗

PubMed2002

Effects of chronic caloric restriction on mitochondrial respiration in the ischemic reperfused rat heart.

Dietary restriction increases life span and delays the development of age-related diseases in rodents. We have recently demonstrated that chronic dietary restriction is beneficial on recovery of heart function following ischemia. We studied whether the metabolic basis of this benefit is associated with alterations in mitochondrial respiration. Male Wistar rats were assigned to an ad libitum-fed (AL) group and a food restricted (FR) group, in which food intake was reduced to 55% of the amount consumed by the AL group. Following an 8-month period of restricted caloric intake, isolated working hearts perfused with glucose and high levels of fatty acids were subjected to global ischemia followed by reperfusion. At the end of reperfusion, total heart mitochondria respiration was assessed in the presence of pyruvate, tricarboxylic acid intermediates, and palmitoylcarnitine. Recovery of heart function following ischemia was greater in FR hearts compared to AL hearts. Paralleling these changes in heart function was an increase in state 3 respiration with pyruvate. The respiratory control ratios in the presence of pyruvate and tricarboxylic acid intermediates were higher in FR hearts compared to AL hearts, indicating well-coupled mitochondria. Overall energy production, expressed as the ADP:O ratio and the oxidative phosphorylation rate, was also improved in FR hearts. Our results indicate that the beneficial effect of FR on recovery of heart function following ischemia is associated with changes in mitochondrial respiration.

Adenosine Diphosphate↗

PubMedDate not supplied

Distinct roles of processes modulated by histone deacetylases Rpd3p, Hda1p, and Sir2p in life extension by caloric restriction in yeast.

Caloric restriction has been demonstrated to extend life span and postpone aging in a variety of species. The recent extension of the caloric restriction paradigm to yeast places the emphasis of the search for the longevity effectors at the cellular level. To narrow the range of potential effectors of the caloric restriction response, we have examined the effects of the histone deacetylases Rpd3p, Hda1p, and Sir2p, which have distinguishable but partially overlapping influences on global patterns of gene expression, on the life extension afforded by caloric restriction. Deletion of the RPD3 gene extended life span, and there was no additive effect of caloric restriction. Deletion of HDA1 had no effect of its own on longevity but acted synergistically with caloric restriction to increase life span. SIR2 deletion shortened life span but did not prevent extension of life span by caloric restriction. The results suggest that Rpd3p affects both processes that play an obligate and those that play a synergistic role in life extension by caloric restriction, while Hda1p and Sir2p affect processes that are not the obligate longevity effectors of caloric restriction but instead synergize with them, although in opposite directions. From the known patterns of gene expression elicited by rpd3delta, hda1delta, and sir2delta, we propose that the major longevity effectors of caloric restriction in yeast involve carbohydrate/energy metabolism and mitochondrial function.

Energy Metabolism↗

PubMed1993

Effect of restricted caloric intake on the development of the azoxymethane-induced glutathione S-transferase placental form positive hepatocellular foci in male F344 rats.

The modifying effect of 30% caloric restriction on the occurrence of azoxymethane (AOM)-induced glutathione S-transferase placental form (GST-P) positive hepatocellular foci was investigated in male F344 rats. Starting at 5 weeks of age, groups of animals were fed ad libitum a high-fat (23.5%) semipurified diet. At 7 weeks of age, all animals except the vehicle-treated groups were s.c. injected with AOM (15 mg/kg body wt., once weekly for 2 weeks). Four days after the second injection, groups of animals were continued on high-fat diet and fed ad libitum (ad libitum group) whereas other groups were restricted to 70% of total calories (calorie-restricted group) consumed by the ad libitum group, but received the same amounts of fiber, vitamins and minerals. Thirty-two weeks after AOM injections, all animals were necropsied and livers were sectioned and stained for GST-P by a immunohistochemical technique for quantitative analysis of enzyme altered foci of the liver. Comparing AOM treated groups. The density and the unit area of enzyme altered foci were significantly lower in the calorie-restricted group (3.84 +/- 1.55/cm2, 7.96 +/- 5.43%) than in the ad libitum group (10.14 +/- 3.62/cm2, 28.11 +/- 12.33%). The size of foci was also reduced in the calorie-restricted group (17.15 x 10(-3) mm2 vs. 32.36 x 10(-3) mm2). The incidence and density of hepatocellular foci in rats fed calorie restricted diet were significantly lower than those in rats fed ad libitum, comparing vehicle-treated groups. These results indicate that calorie restriction inhibited the occurrence of both of spontaneous and AOM induced GST-P positive foci in rats.

Animals↗

PubMed1993

Evidence for success of caloric restriction in weight loss and control. Summary of data from industry.

Data voluntarily supplied by industry were examined to evaluate the success of commercial weight loss programs and products. Information about the safe loss of weight, the maintenance of this lowered weight, and resultant health benefits were reviewed. Information was received from companies that produce over-the-counter preparations designed for persons with a small weight loss goal and from physician-supervised programs for morbidity obese persons placed on very-low-calorie diets. Regardless of the products used, successful weight loss and control was limited and required individualized programs consisting of restricted caloric intake, behavior modification, and exercise. Although some manufacturers of physician-supervised weight loss products for obese persons hav defined the effectiveness of their programs with controlled clinical studies, other industry programs have only begun to accurately assess their effectiveness or safety. Given the importance to public health of reducing obesity, rigorous studies on current weight control practices should be pursued aggressively.

Behavior Therapy↗

PubMed1987

Effect of restricted caloric intake on azoxymethane-induced colon tumor incidence in male F344 rats.

The effect of 30% caloric restriction on azoxymethane (AOM)-induced colon carcinogenesis was investigated in male F344 rats. Starting at 5 weeks of age, groups of animals were fed ad libitum a high-fat (23.5%) semipurified diet. At 7 weeks of age, all animals except the vehicle-treated groups were s.c. injected with AOM (15 mg/kg body wt, once weekly for 2 weeks). Four days after the second AOM injection, groups of animals were continued on high-fat diet and fed ad libitum (ad libitum group) whereas other groups were restricted to 70% of total calories (calorie-restricted group) consumed by the ad libitum group, but received same amounts of fiber, vitamins, and minerals. Thirty-two weeks after AOM injections, all animals were necropsied. The animals in the calorie-restricted group developed significantly fewer colon tumors and had a lower colon tumor incidence than did the rats in the ad libitum group. The size of colon tumors was also reduced in the calorie-restricted group.

Animals↗

PubMed1999

Pleiotropic effects of growth hormone and insulin-like growth factor (IGF)-1 on biological aging: inferences from moderate caloric-restricted animals.

Moderate caloric restriction (60% of ad libitum intake) is an important model to investigate potential mechanisms of biological aging. This regimen has been reported to decrease the number of pathologies and increase life span in all species tested to date. Although moderate caloric restriction induces a wide range of physiological changes within the organism, adaptive changes within the endocrine system are evident and serve to maintain blood levels of glucose. These alterations include an increase in growth hormone secretory dynamics and a decline in plasma levels of IGF-1. These endocrine compensatory mechanisms can be induced at any age, and we have proposed that these alterations mediate some of the beneficial aspects of moderate caloric restriction. Numerous studies indicate that growth hormone and IGF-1 decrease with age and that administration of these hormones ameliorates the deterioration of tissue function evident in aged ad libitum-fed animals, suggesting that the absence of these hormones contributes to the phenotype of aging. Nevertheless, IGF-1 is an important risk factor in age-related pathologies including lung, breast, and prostate cancer. From these studies, we propose that endocrine compensatory mechanisms induced by moderate caloric restriction (including increased growth hormone and decreased IGF-1) decrease the stimulus for cellular replication, resulting in a decline in pathologies and increased life span observed in these animals. These findings have important implications for potential mechanisms of moderate caloric restriction and suggest that neuroendocrine compensatory mechanisms exert a key role on the actions of moderate caloric restriction on life span.

Aging↗

PubMed1998

Caloric restriction prevents age-related decline in skeletal muscle dihydropyridine receptor and ryanodine receptor expression.

The dihydropyridine receptor (DHPR), a voltage-gated L-type Ca2+ channel, and the Ca2+ release channel/ryanodine receptor isoform-1 (RyR1) are key molecules involved in skeletal muscle excitation-contraction coupling. We have reported age-related decreases in the level of DHPR expression in fast- and slow-twitch muscles from Fisher 344 cross Brown Norway (F344BNX) rats (Renganathan, Messi and Delbono, J. Membr. Biol. 157 (1997) 247-253). Based on these studies we postulate that excitation-contraction uncoupling is a basic mechanism for the decline in muscle force with aging (Delbono, Renganathan and Messi, Muscle Nerve Suppl. 5 (1997) S88-92). In the present study, we extended our studies to older ages and we intended to prevent or retard excitation-contraction uncoupling by restricting the caloric intake of the F344BNX rats from 16 weeks of age. Three age groups, 8-, 18-, and 33-month old caloric restricted rats, were compared with ad libitum fed animals. The number of DHPR and RyR1 and DHPR/RyR1 ratio (an index of the level of receptors uncoupling) in skeletal muscles of 8-month and 18-month rats was not significantly different in either ad libitum fed or caloric restricted rats. However, the age-related decrease in the number of DHPR, RyR1 and DHPR/RyR1 ratio observed in 33-month old ad libitum fed rats was absent in 33-month old caloric restricted rats. These results suggest that caloric restriction prevents age-related decreases in the number of DHPR, RyR1 and DHPR/RyR1 ratio observed in fast- and slow-twitch rat skeletal muscles.

Aging↗

PubMed1996

Adaptations of intestinal nutrient transport to chronic caloric restriction in mice.

Lifelong caloric restriction increases median and maximum life span and retards the aging process in many organ systems of rodents. Because the small intestine absorbs a reduced amount of nutrients each day, does lifelong caloric restriction induce adaptations in intestinal nutrient transport? We initially compared intestinal transport of sugars and amino acids between 24-mo-old mice allowed free access to food [ad libitum (AL)] and those provided a calorically restricted [40% less than ad libitum (CR)] diet since 3 mo of age. We found that CR mice had significantly greater transport rates for D-glucose, D-fructose, and several amino acids and had significantly lower villus heights. Total intestinal absorptive capacities for D-glucose, D-fructose, and L-proline were each 40-50% greater in CR mice; absorptive capacity normalized to metabolic mass (body weight 0.75) was approximately 80% greater in CR mice. Comparison of uptakes in aged AL and CR mice with previously published results in young AL mice suggests that caloric restriction delays age-related decreases in nutrient transport. In contrast to published studies in hibernation and starvation, chronic caloric restriction enhances not only uptake per milligram but also uptake per centimeter. We then switched 24-mo-old AL mice to a calorie-restricted diet for 1 mo and found that short-term caloric restriction has no effect on intestinal nutrient transport, intestinal mass, and total absorptive capacity. Thus chronic but not short-term caloric restriction increases intestinal nutrient transport rates in aged mice, and the main mechanism underlying these increases is enhanced transport rates per unit intestinal tissue weight.

Adaptation, Physiological↗

PubMed1999

Caloric restriction and aging.

Caloric restriction in species with a short life span has shown it can increase median and maximum life expectancy and reduce or delay the onset of most age-related diseases. The remarkable reproducibility of the phenomenon irrefutably proves its validity and makes caloric restriction one of the most frequently studied paradigms in experimental research on aging.

Aging↗