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 271 records · Page 15Linked to original sources

PubMed1997

Caloric restriction causes secretagogue specific changes of gastric acid secretion in rats.

The purpose of this study was to examine the effects of short-term caloric restriction (CR) for 4, 8 and 16 weeks on gastric acid secretion in rats. CR rats fed 60% of normal food intake for 4, 8 or 16 weeks and then prepared with gastric fistulas. Histamine- and carbachol-stimulated gastric acid secretion were significantly (P < 0.05) decreased after more than 4 weeks and 8 weeks of caloric restriction, respectively. In contrast, gastrin-stimulated acid secretion was unaffected by CR. The 1-h-integrated acid output to a submaximal dose of gastrin (40 micrograms.kg-1) was significantly higher than that of histamine (5 mg.kg-1) after 8 weeks of CR (63 +/- 13 and 27 +/- 4 microEq.h-1, respectively). Gastrin treatment (5 micrograms.kg-1.h-1) of CR rats restored the gastric acid responses to both histamine and carbachol. These results suggest that CR can selectively decrease the gastric acid responses to both histamine and carbachol by depletion of the endogenous tissue stores of gastrin. More importantly, these results indicate that under an in vivo gastrin-diminished condition, histamine is not the final secretagogue for gastric acid secretion.

Animals↗

PubMed2006

Caloric restriction increases longevity substantially only when the reaction norm is steep.

Evolutionary theory leads to the general expectation that dietary restriction will often result in increased survival probabilities, and thus increased lifespan. The reaction norm is a basic tool of evolutionary analysis that quantifies the relationship between environmental parameters and functional characters, including reproduction and longevity. In rodents, the reaction norm connecting adult longevity to caloric intake is fairly steep; small changes in intake lead to large changes in longevity. 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. In theory, however, reaction norms are expected to evolve for fitness related characters such as reproduction and survival. It has been shown experimentally in Drosophila that dietary reaction norms readily evolve in the laboratory, suggesting that they can do so among mammals as well, particularly over the millions of years since contemporary rodents and primates last shared a common ancestor. Our previous work crudely estimates that the dietary reaction norms of rodents and humans have diverged substantially, with a very flat dietary reaction norm for human longevity. These general principles and our specific results suggest that the benefits from human caloric restriction would be minor.

Adaptation, Physiological↗

PubMed2005

The ageing phenome: caloric restriction and hormones promote neural cell survival, growth, and de-differentiation.

The phenome represents the observable properties of an organism that have developed under the continued influences of both genome and environmental factors. Phenotypic properties are expressed through the functions of cells, organs and body systems that operate optimally, close to equilibrium. In complex organisms, maintenance of the equilibrium is achieved by the interplay of several regulatory mechanisms. In the elderly, dynamic instability may lead to progressive loss of normal function, failure of adaptation and increased pathology. Extensive research (reported elsewhere in this journal) has demonstrated that genetic manipulations of endocrine signaling in flies, worms and mice increase longevity. Another effective strategy for prolonging the lifespan is caloric restriction: in data presented here, the persistence of estrogen-sensitive cells in the hypothalamus of caloric restricted 22-month-old female mice, may explain the persistence of reproductive function at an age, when reproductive function has long ceased in ad libitum fed controls. Still another strategy utilizes the effects of epidermal growth factor (EGF) to promote in vitro proliferation of neuroglia, astrocytes and oligodendrocytes. Their subsequent de-differentiation generates immature precursor cells potentially capable of differentiating into neuroblasts and neurons. These and other examples suggest that, in terms of functional outcomes, "the genome proposes but the phenome disposes".

Aging↗

PubMedDate not supplied

Comparison of clofibrate and caloric restriction on kinetics of very low density lipoprotein triglycerides.

This study of 12 patients with mild-to-moderate hypertriglyceridemia compares the mechanisms of triglyceride (TG) lowering by caloric restriction and by clofibrate. Turnover rates of very low density lipoprotein triglycerides (VLDL-TG) were determined by using 3H-glycerol as a precursor. Radioactivity-time curves of VLDL-TG were analyzed with a multicompartmental model. Hypertriglyceridemia in these patients was due mainly to overproduction of VLDL-TG. Clofibrate therapy for 1 month had a variable effect on VLDL-TG levels. A group of relatively poor responders to the drug had a mild increase in the fractional catabolic rate (FCR) of VLDL-TG, but no change in production rates. The remaining patients were relatively good responders; they had increased FCR and modest reductions in synthetic rates of VLDL-TG. However, clofibrate largely failed to correct the primary defect in this group of patients, namely, the overproduction of VLDL-TG. Almost all patients responded to 1 month of caloric restriction (1000 cal/day) with marked reductions in VLDL-TG levels. The major response to reduced caloric intake was a decrease in production of VLDL-TG, although FCR was also increased to some extent. Despite these differences in mechanisms for VLDL-TG lowering, both regimens tended to raise levels of LDL and HDL.

Adult↗

PubMed1999

Caloric restriction leads to regional specialisation of adipocyte function in the rat.

The study analysed the responses of three metabolic parameters in five distinct adipose tissue depots to caloric restriction (4 weeks) in the rat. The aims were to evaluate whether specific adipose tissue depots were recruited for triacylglycerol (TAG) storage and/or mobilisation, and to determine to what extent specific adipose tissue depots exhibited preferences for the source of fatty acid (FA) for TAG storage. Caloric restriction led to a general enhancement of the response of lipoprotein lipase (LPL), FA synthesis and glucose utilisation to a meal. Effects were particularly marked in the parametrial, perirenal and interscapular depots compared with mesenteric and subcutaneous depots. There was no evidence that individual depots selectively expressed a preference for the pathways concerned with the generation of FA for storage (the exogenous (LPL) and the endogenous (synthesis) pathway). However, the temporal sequence of activation of these pathways differed in a manner consistent with a switch from preponderant use of FA produced via de novo synthesis during the very early phase of feeding towards later use of FA derived from circulating TAG. The overall excursions in insulin levels observed in the calorie-restricted rats were comparable to those found in free-feeding rats, but the magnitude and the rapidity of the individual metabolic responses of the adipocyte were augmented. The data are consistent with a general enhancement of insulin sensitivity and responsiveness in adipose tissue of calorie-restricted rats, together with adaptive regional specialisation of adipocyte function. These adaptations would be predicted to facilitate the immediate conservation of dietary nutrients by promoting their storage as the FA or glycerol moieties of adipose tissue TAG and thereby to ensure the regulated release of FA and glycerol from adipose tissue in accordance with the requirement for glucose conservation and/or production.

Adipocytes↗

PubMed1998

Effects of caloric restriction or augmentation in adult rats: longevity and lesion biomarkers of aging.

Caloric restriction (CR) initiated in young rodents has been thoroughly documented to enhance longevity, but its efficacy when introduced at older ages has not been well investigated. Cohorts of 18- and 26-month-old male F344 x BN F1 hybrid rats were fed either: 1) NIH-31 meal (C); 2) vitamin and mineral fortified NIH-31 meal (R); or 3) vitamin and mineral fortified NIH-31 meal supplemented with corn oil and sweetened condensed milk (S). The C control rats were fed ad libitum, R rats were restricted to 32% of the caloric intake of the controls, and S rats were allowed to consume not more than 8% more calories than C rats. After 6 weeks, the average weights were significantly different between all diet and age groups. Although calorie manipulation altered body weight, no significant effect of the dietary intervention on longevity was found. The average lesion burden, including tumor burden and prevalence of nearly all commonly occurring lesions, were comparable between the groups. Thus, the manipulation of weight at ages beyond middle age has a much less profound impact than similar interventions during growth and maturation in rats.

Adrenal Gland Neoplasms↗

PubMed2003

In vivo assessment of the mitochondrial response to caloric restriction in obese women by the 2-keto[1-C]isocaproate breath test.

The 2-keto[1-(13)C]isocaproate breath test has been proposed as a tool to detect mitochondrial dysfunction in alcoholic liver disease. The aim of this study was to evaluate if the 2-keto[1-(13)C]isocaproate breath test could detect in vivo dynamic changes on mitochondrial activity due to caloric restriction in obese women. Fifteen obese women (body mass index [BMI] > 30 kg/m(2)) participated in the study at baseline. Ten of these women agreed to participate on a diet program to induce body weight loss. Fifteen lean women (BMI < 25 kg/m(2)) were included as a control group. The breath test was performed by the oral administration of the tracer measuring (13)CO(2) enrichment in breath before and after ingestion using isotope ratio mass spectrometry. Body composition, resting energy expenditure, and plasma levels of insulin and leptin were measured. There were no relationships observed between the 2-keto[1-(13)C]isocaproate breath test and the plasma insulin (before diet: P =.863; after diet: P =.879), or leptin (before diet: P =.500; after diet: P =.637). In obese women before treatment, kilograms of fat free mass (P =.108), resting energy expenditure adjusted for body composition (P =.312), and the 2-keto[1-(13)C]isocaproate breath test (P =.205) were similar in comparison to lean women. However, 2-keto[1-(13)C]isocaproate oxidation tended to increase after dieting and was significantly higher than in controls (P =.015). These data suggest that the 2-keto[1-(13)C]isocaproate breath test reflected the adaptive modifications in mitochondrial oxidation in response to caloric restriction in obese women.

Adolescent↗

PubMed2005

Effects of age and caloric restriction on lipid peroxidation: measurement of oxidative stress by F2-isoprostane levels.

The free radical theory of aging proposes that the accumulation of oxidative damage is a key component of the aging process. The discovery of F2-isoprostanes (F2-isoPs) and their establishment as a sensitive and accurate biomarker of lipid peroxidation represents a major advance for measuring the oxidative stress status of an organism. We have shown that plasma free and total (free plus esterified) F2-isoPs increase with age (185% and 66%, respectively), and that these increases are reduced by life-extending caloric restriction (50% and 23%, respectively). In addition, we found that levels of esterified F2-isoPs increase 68% with age in liver, and 76% with age in kidney. Caloric restriction modulated the age-related increase, reducing the esterified F2-isoPs levels 27% in liver and 35% in kidney. These age-related increases in esterified F2-isoPs levels correlate well with DNA oxidation, as measured by 8-oxodeoxyguanosine production demonstrating that F2-isoPs are an excellent biomarker for age-related changes in oxidative damage to membranes.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2006

Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice.

Caloric restriction (CR), which improves health and increases longevity, was studied as a therapy in a hexosaminidase beta knockout mouse model of Sandhoff disease (SD), an incurable neurodegenerative disease involving accumulation of brain ganglioside GM2 and asialo-GM2 (GA2). Adult mice were fed a rodent chow diet either ad libitum (AL) or restricted to reduce body weight by 15-18% (CR). Although GM2 and GA2 were elevated, no significant differences were seen between the Hexb-/- and the Hexb+/- mice for most brain phospholipids and cholesterol. Cerebrosides and sulfatides were reduced in the Hexb-/- mice. In addition, rotorod performance was significantly worse in the Hexb-/- mice than in the Hexb+/- mice. CR, which decreased circulating glucose and elevated ketone bodies, significantly improved rotorod performance and extended longevity in the Hexb-/- mice but had no significant effect on brain lipid composition or on cytoplasmic neuronal vacuoles. The expression of CD68 and F4/80 was significantly less in the CR-fed than in the AL-fed Hexb-/- mice. We suggest that the CR delays disease progression in SD and possibly in other ganglioside storage diseases through anti-inflammatory mechanisms.

3-Hydroxybutyric Acid↗

PubMed2003

Caloric restriction increases gluconeogenic and transaminase enzyme activities in mouse liver.

Long-term caloric restriction (CR) has been shown to extend maximum life span in laboratory rodents. We investigated the activities of gluconeogenic and transaminase enzymes in the livers of old and young mice fed either control or calorie-restricted diets. Livers were sampled 48 h after the last scheduled feeding time. Old mice on CR showed significant increases in the activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase when compared with controls, indicating increased gluconeogenesis. Increased activities of tyrosine, tryptophan, histidine, phenylalanine, alanine and aspartate transaminases, as well as of malate and glutamate dehydrogenases were also observed, while branched-chain amino acid transaminase was unchanged. Young mice on CR showed a significant increase only in the phosphoenolpyruvate carboxykinase activity in the gluconeogenic pathway, while transaminases were increased significantly, except for tryptophan and branched-chain amino acid transaminases. Glutamate dehydrogenase also showed increased activity but malate dehydrogenase was unchanged. Increases in the level of acetyl-CoA and [Acetyl-CoA]/[CoA] ratio were observed only in the old CR mice. Our results demonstrate increased gluconeogenic activity in CR mice and are consistent with a state of increased hepatic gluconeogenesis and protein turnover during CR.

Acetyl Coenzyme A↗

PubMed1983

Clofibrate, caloric restriction, supersaturation of bile, and cholesterol crystals.

Lipid composition, cholesterol saturation, and cholesterol crystal formation of gallbladder bile were studied in seven type-IV hyperlipoproteinemic subjects who did not have gallstones. Thereafter, biliary cholesterol solubilization was overloaded, first by clofibrate and then by caloric restriction treatment. Initially increased cholesterol saturation was still increased by both clofibrate and caloric restriction treatment, but none of the subjects developed cholesterol crystals in bile, indicating that they had a mechanism to maintain cholesterol in solution in the bile despite remarkable supersaturation. This suggests that the patients who are at risk of developing gallstones can be better selected by cholesterol crystal analysis of bile samples than by analysis of lipid composition of bile.

Aged↗

PubMed1999

Influence of caloric restriction on the development of atherosclerosis in nonhuman primates: progress to date.

Caloric restriction (CR) has been observed to retard aging processes and extend the maximum life span in rodents. In an effort to evaluate the effect of this nutritional intervention on physiologic variables in higher species, several nonhuman primate trials are ongoing. In particular, a study evaluating the independent effect of CR on the extent of atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys. Therefore, the trial was designed to achieve identical cholesterol intake after animals were randomized to a control group or a calorie-restricted group (30% reduction from baseline caloric intake). The animals were routinely evaluated for glycated proteins, plasma insulin and glucose levels, insulin sensitivity, and specific measures for abdominal fat distribution by CT scans over a 4-year interval. The results from 4 years of intervention demonstrate that CR improves cardiovascular risk factors (such as visceral fat accumulation) and improves insulin sensitivity. In contrast to other primate studies with normolipidemic animals, CR had no independent effects on plasma lipid levels and composition in the presence of equivalent amounts of dietary cholesterol intake. Preliminary analysis of atherosclerotic lesion extent in the abdominal aorta has failed to demonstrate differences between control animals and CR animals. Follow-up studies are being conducted to determine the effect of CR on atherosclerosis extent in coronary and carotid arteries.

Aging↗

PubMed2003

Method for measuring ATP production in isolated mitochondria: ATP production in brain and liver mitochondria of Fischer-344 rats with age and caloric restriction.

The production of ATP is vital for muscle contraction, chemiosmotic homeostasis, and normal cellular function. Many studies have measured ATP content or qualitative changes in ATP production, but few have quantified ATP production in vivo in isolated mitochondria. Because of the importance of understanding the energy capacity of mitochondria in biology, physiology, cellular dysfunction, and ultimately, disease pathologies and normal aging, we modified a commercially available bioluminescent ATP determination assay for quantitatively measuring ATP content and rate of ATP production in isolated mitochondria. The bioluminescence assay is based on the reaction of ATP with recombinant firefly luciferase and its substrate luciferin. The stabilities of the reaction mixture as well as relevant ATP standards were quantified. The luminescent signals of the reaction mixture and a 0.5 microM ATP standard decreased linearly at rates of 2.16 and 1.39% decay/min, respectively. For a 25 microM ATP standard, the luminescent signal underwent a logarithmic decay, due to intrinsic deviations from the Beer-Lambert law. Moreover, to test the functionality of isolated mitochondria, they were incubated with 1 and 5 mM oligomycin, an inhibitor of oxidative phosphorylation. The rate of ATP production in the mitochondria declined by 34 and 83%, respectively. Due to the sensitivity and stability of the assay and methodology, we were able to quantitatively measure in vivo the effects of age and caloric restriction on the ATP content and production in isolated mitochondria from the brain and liver of young and old Fischer-344 rats. In both tissues, neither age nor caloric restriction had any significant effect on the ATP content or the rate of ATP production. This study introduces a highly sensitive, reproducible, and quick methodology for measuring ATP in isolated mitochondria.

Adenosine Triphosphate↗

PubMedDate not supplied

The anti-ageing effects of caloric restriction may involve stimulation of macroautophagy and lysosomal degradation, and can be intensified pharmacologically.

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. Evidence is reviewed showing that CR and reduced insulin of GH-IGF-1 axis may exhibit their effects at least partly by their common stimulatory action on autophagy, the cell repair mechanism responsible for the housekeeping of cell membranes and organelles including the free radical generators peroxisomes and mitochondria. It is shown that the life-long weekly administration of an anti-lipolytic drug may decrease glucose and insulin levels and stimulate autophagy and intensify anti-ageing effects of submaximal CR.

Aging↗

PubMedDate not supplied

The retardation of aging by caloric restriction: its significance in the transgenic era.

The retardation of aging and diseases by caloric restriction (CR) is a widely-studied and robust phenomenon. Recent publications describe transgenic and other mutant rodents displaying lifespan extension, and the rapid pace at which these animals are being generated raises the possibility that the importance of the CR paradigm is declining. Here we discuss these models and evaluate the evidence whether or not the aging process is retarded based on longevity, disease patterns and age-associated biological changes. A comparison to rodents on CR is made. Because CR has been investigated for approximately 70 years with increasing intensity, there exists extensive data to document aging retardation. In contrast, for nearly all of the genetically abnormal models of lifespan extension, such data are minimal and often unconvincing; additional studies will be required to validate these strains as suitable models for aging research.

Aging↗

PubMed1997

Caloric restriction increases HDL2 levels in rhesus monkeys (Macaca mulatta).

Caloric restriction (CR) prolongs the life of rodents and other small animals, but the benefits of CR for primates and people are as yet unknown, and mechanisms by which CR may slow aging remain unidentified. A study of rhesus monkeys, Macaca mulatta, is underway to determine if CR might prolong life span in primates and to evaluate potential mechanisms for life prolongation. Thirty rhesus monkeys in three age cohorts, restricted to 70% of ad libitum calorie intake for 6-7 yr, were compared with 30 controls. Plasma lipid, lipoprotein, and high-density lipoprotein (HDL) apolipoproteins and subfractions were measured and compared with weight, percent fat, glucose, and insulin level. CR caused decreased triglyceride levels in adult monkeys and increased levels of HDL2b, the HDL subfraction associated with protection from atherosclerosis. Multivariate statistical analyses showed that differences in lipid and lipoprotein levels occurring with CR could be accounted for, at least in part, by decreased body mass and improved glucose regulation. These studies have used a novel dietary modification paradigm in nonhuman primates focused on calorie reduction. Results suggest that CR, as mediated by its beneficial effect on body composition and glucose metabolism, could prolong human life by decreasing the incidence of atherosclerosis.

Aging↗

PubMed1995

The effect of caloric restriction on lipofuscin accumulation in mouse brain with age.

Caloric restriction (CR), has been shown to extend average and maximum lifespan in rodents and other animals as well as to delay a wide variety of manifestations of aging. The purpose of this study was to further elucidate the relationship between lipofuscin (LF) accumulation and the aging process by examining the effect of lifelong CR on LF accumulation in brain cells. Specifically, 1) we include age groups of CR (CR1 approximately equal to 90 kcal/wk and CR2 approximately equal to 58 kcal/wk) and ad libidum fed (AL; approximately 120 kcal/wk) mice including groups at maximum lifespan; 2) CR was the major dietary manipulation; 3) LF was identified using EM; 4) LF was quantified by areal measurement; and 5) the results were analyzed by inferential statistics. We have found that 1) LF increased with age and 2) that animals in the CR2 group had significantly less overall LF in the perikarya of the granule cells of the dentate gyrus when compared to CR1 or AL animals at equivalent ages. In addition, CR2 mice at maximum lifespan (45 mo.) had slightly less LF than did CR1 or AL mice at their maximum lifespans (36 mo.). Our results clearly demonstrate that CR (at 52%, but not 25% of AL diet) retards the overall accumulation of LF with time and, further, suggest that LF accumulation is not simply a linear function of age.

Aging↗

PubMed2003

Influence of age and caloric restriction on liver glycolytic enzyme activities and metabolite concentrations in mice.

The influence of caloric restriction (CR) from 2 months of age on the activities of liver glycolytic enzymes and metabolite levels was studied in young and old mice. Livers were sampled 48 h after the last scheduled feeding time. Old mice on CR showed significant decreases in the activities of all the enzymes studied, except for aldolase, triosephosphate isomerase and phosphoglycerate mutase, which were unchanged. The metabolites glucose, glucose-6-phosphate, fructose-6-phosphate, pyruvate and lactate were lower while fructose-1,6-bisphosphate, glyceraldehyde-3-phosphate, dihydroxyacetone phosphate, 3-phosphoglycerate and phosphoenolpyruvate were increased in old CR. Young mice on CR also showed reduced enzyme activities, except for aldolase, triosephosphate isomerase and enolase which were unchanged when compared with young controls. The metabolites glucose, glucose-6-phosphate, fructose-6-phosphate and pyruvate were decreased when compared with young controls, while phosphoenolpyruvate was increased. Ketone bodies increased (65%) in old, but not young, CR mice while fructose-2,6-bisphosphate decreased in both young (22%) and old CR (28%) mice. The results indicate that decreased hepatic glucose levels in CR mice are associated with decreased enzyme activities but not a uniform decrease in metabolite levels. Increased ketone body levels indicate increased utilization of non-carbohydrate fuels while decreased fructose-2,6-bisphosphate level suggests its importance in the control of glycolysis in CR.

3-Hydroxybutyric Acid↗