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Results for “Dietary restriction”

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At least 19 recordsLinked to original sources

PubMed1992

Protection of DNA damage by dietary restriction.

Dietary restriction is known to retard the aging processes and delay the onset of age-related neoplastic diseases. The mechanisms underlying these remarkable actions of nutritional intervention are not known in spite of recently intensified research efforts. However, the last couple of years' research on dietary restriction produced strong evidence indicating that its effective antiaging actions might be related to its ability to modulate free radical damage. In the present study, DNA damage and attenuation of the damage by dietary restriction were assessed by measuring 8-hydroxydeoxyguanosine 8-OH dG) in both nuclear DNA (nuDNA) and mitochondrial DNA (mitDNA) fractions. The data show that substantially more damage (approximately 15 times) occurred in mitDNA compared to nuDNA. More interestingly, the DNA damage was significantly attenuated in dietarily restricted rats.

Animals↗

PubMed2005

Behavioral, physical, and demographic changes in Drosophila populations through dietary restriction.

Dietary restriction (DR) is a valuable experimental tool for studying the aging process. Primary advancement of research in this area has relied on rodent models, but attention has recently turned toward Drosophila melanogaster. However, little is known about the baseline effects of DR on wild-type Drosophila and continued experimentation requires such information. The findings described here survey the effects of DR on inbred, wild-type populations of Canton-S fruit flies and demonstrate a robust effect of diet on longevity. Over a circumscribed range of dietary conditions, healthy lifespan varies by as much as 121% for wild-type Drosophila females. Significant differences are also observed for male flies, but the magnitude of the DR effect is less robust. Mortality analyses of the survivorship data reveal that this variation in lifespan can be attributed to a modulation of the rate parameter for the mortality function - a change in the demographic rate of aging. Since the feeding of fruit flies is less easily controlled than that of rodents, this research also addresses the validity of applying a DR model to Drosophila populations. Feeding and body weight data for flies given the various dietary conditions surveyed indicate that Drosophila on higher-calorie diets consume a similar volume of food to those on a low-calorie diet, resulting in different levels of calorie intake. Fertility and activity levels demonstrate that the diets surveyed are comparable, and that increasing the calorie content of laboratory food up to twice the normal concentration is not pathologic for experimental fly populations.

Aging↗

PubMedDate not supplied

Dietary restriction.

Dietary restriction (DR) slows the rate of actuarial aging of rats and mice and in addition retards and/or delays many phenotypic characteristics of aging such as the age-associated deterioration of physiological systems and the occurrence and progression of age-associated disease. These antiaging actions result from a reduction of energy intake by the animal but are not due to a decrease in metabolic rate per unit of lean body mass. However, there is evidence that altered characteristics of fuel use (but not the intensity of fuel use) may underlie the antiaging action of DR. There is also evidence that DR has a general protective action in regard to damage caused by acute stressors; possibly a similar protective action in regard to damage caused by prolonged, low intensity aging processes plays a major role in the antiaging action of DR.

Aging↗

PubMed2003

Strain variation in the response of body temperature to dietary restriction.

Dietary restriction (DR, also referred to as calorie restriction, energy restriction, and food restriction) retards senescence and increases longevity in mammals. DR also lowers mean body temperature (T(b)), and thus mean T(b) might be useful as a covariate of DR-induced life extension. Indeed, lower T(b) could itself underlie some of the beneficial life-extension effects that occur during DR. To assess the relationship between lower T(b) during DR and life extension, we asked whether significant strain variation exists in the T(b) response of mice being fed 60% ad libitum (AL). Individually-housed, female mice from 28 strains, representing a genealogically diverse sample of the classical inbred strains, were directly compared. The mean T(b)s in response to DR exhibited highly significant strain variation, ranging from 1.5 degrees C below normal to a phenomenal 5 degrees C below normal. This variation was not explained by differences in loss of thermoregulation, AL adiposity, sensitivity to a nonadaptive hypothermia, motor activity, thermal arousal, absolute food intake, or efficacy of nutrient extraction. The variation in strain mean T(b) was also present in the absence of torpor. This strain variation could be used to critically test whether lower T(b) is a covariate of life extension during DR.

Adipose Tissue↗

PubMed1996

Reduced immune responses in rhesus monkeys subjected to dietary restriction.

Dietary restriction (DR) has emerged as a major paradigm in experimental gerontology. The effects of DR on rodents are numerous and include reduced rates of immunologic aging, delayed morbidity, and increases in longevity. The effects of DR on primate species remain largely unknown. We began a randomized trial of long-term, adult-onset DR in rhesus monkeys (Macaca mulatta) in 1989. This report describes some early differences in immunologic function after two to four years of DR. Peripheral blood mononuclear cells were studied for mitogen-induced proliferation, natural killer (NK) cell lysis, and expression of cell surface antigens. Antibody response to influenza vaccine and the number of peripheral blood lymphocytes were also measured. Unexpectedly, concanavalin A and pokeweed mitogen response measures were reduced in restricted monkeys compared to controls (p < or = .01). NK activity and antibody responses were also reduced (p < .05). Neither cell surface antigens nor peripheral blood lymphocyte counts appear affected by DR thus far.

Aging↗

PubMed2004

Quantitative trait Loci specifying the response of body temperature to dietary restriction.

Dietary restriction (DR) retards aging and mortality across a variety of taxa. In homeotherms, one of the hallmarks of DR is lower mean body temperature (T(b)), which might be directly responsible for some aspects of DR-mediated life extension. We conducted a quantitative trait locus (QTL) analysis of the response of T(b) to DR in mice using a panel of 22 LSXSS recombinant inbred strains, tested in two cohorts. T(b) in response to DR had a significant genetic component, explaining approximately 35% of the phenotypic variation. We mapped a statistically significant QTL to chromosome 9 and a provisional QTL to chromosome 17, which together accounted for about two thirds of the genetic variation. Such QTLs could be used to critically test whether the response of T(b) to DR also affects the response of life extension. In addition, this study demonstrates the feasibility of trying to map QTLs that affect other physiological responses to DR, including the life extension response. Importantly, the genes underlying such QTLs would be causal factors affecting these responses and could be identified by positional cloning.

Aging↗

PubMed2005

Microarray evaluation of dietary restriction.

Dietary restriction (DR) extends the life span and retards many age-related cellular and molecular changes in laboratory rodents. However, neither its underlying mechanism nor the limits of its action are fully understood. In this review, we assessed the effect of DR on gene expression in vertebrate and invertebrate animals using data generated by microarrays. Altered genes in DR mice reported in 15 articles published since 1999 were compared. A comparison of altered genes by DR in mice, rats, pigs, monkeys, yeast, and flies showed no common gene altered by DR among different species. It seems that individual genes altered in the expression by DR were constrained within species. When we compared the functions of altered genes across all species, we found that certain functions such as metabolism, energy metabolism, stress and immune response, cell growth, and transcription regulation were shared among species. Although individual genes seem to be affected by DR differently among species, the overall physiologic influence of DR may be similar.

Animals↗

PubMed1990

Ethane production rate in vivo is reduced with dietary restriction.

Dietary restriction without malnutrition prolongs life and has a beneficial effect on age-related diseases and metabolic derangements. To test the effect of food restriction on ethane production rate, ethane exhalation was measured in rats with partial food restriction. Ethane production rate in room air in rats fed 60% of food consumed by ad libitum-fed animals for 2 wk was significantly reduced (3.50 +/- 0.25 vs. 5.21 +/- 0.34 pmol.min-1.100 g body wt-1, P less than 0.01). In 100% oxygen, ethane production in food-restricted rats was not different from that of ad libitum-fed rats (21.81 +/- 1.25 vs. 19.57 +/- 1.89 pmol.min-1.100 g-1). Fifteen hours of fasting compared with ad libitum feeding reduced ethane production modestly in room air (4.37 +/- 0.45 vs. 5.21 +/- 0.34 pmol.min-1.100 g-1) and more significantly in 100% oxygen (12.37 +/- 0.78 vs. 19.57 +/- 1.89 pmol.min-1.100 g-1). Thus, in 100% oxygen, 15 h of fasting, compared with ad libitum feeding, resulted in an approximately 40% decrease in ethane production rate. It is concluded that short-term food restriction significantly reduces ethane exhalation rate in rats when measured in room air.

Animals↗

PubMed2003

Energy expenditure of rhesus monkeys subjected to 11 years of dietary restriction.

Dietary restriction (DR) is currently the only paradigm that has consistently extended maximal life span and reduced the onset of age-related chronic diseases in all of the nonprimate species tested. Although it is controversial, some investigators have suggested that the underlying mechanisms may be mediated by adaptations in energy expenditure. We evaluated the extent to which DR alters energy metabolism in a unique cohort of rhesus monkeys submitted to DR for 11 yr. Total energy expenditure (doubly labeled water), resting energy expenditure (REE; indirect calorimetry), and nonbasal energy expenditure (calculated by difference) were measured in DR (n = 12) and control (n = 11) animals. Body composition was determined by dual energy x-ray absorptiometry. Both fat mass and fat-free mass were lower in the restricted animals (56 and 12%, respectively). DR induced a 17% lower total energy expenditure that was attributable to a 20% decrease in REE without changes in the nonbasal energy expenditure. Adjusted for fat-free mass, REE was 13% lower with DR (-250 kJ/d). Taken together with a reanalysis of previous DR experiments published in humans, rodents, and monkeys, these results suggest that DR may lower REE independent of the DR-induced changes in body composition. Whether this reduction in REE contributes to the life-extending properties of DR warrants further analysis, but it suggests that the long-standing debate regarding DR effects on metabolic rates may derive from the lack of consensus on how to adjust for body size and composition.

Animals↗

PubMedDate not supplied

The relative protective effects of moderate dietary restriction versus dietary modification on spontaneous cardiomyopathy in male Sprague-Dawley rats.

The relative protective effects of modifying dietary protein, fat, fiber, and energy content vs moderate food or dietary restriction (DR) on spontaneous cardiomyopathy of Charles River male Sprague-Dawley (SD) rats was evaluated at 1 and 2 years. For 2 years, SD rats were fed Purina Rodent Chow 5002 (21.4% protein, 5.7% fat, 4.1% fiber, 3.1 kcal/g) or a modified rodent chow 5002-9 (13.6% protein, 4.6% fat, 15.7% crude fiber, 2.4 kcal/g) ad libitum (AL) or by moderate DR at approximately 65% of the caloric intake of the AL group fed the 5002 diet. Serum lipids, carcass composition, and organ weights were evaluated and hearts were qualitatively and quantitatively examined microscopically for male SD rats at 1 and 2 years. Cardiomyopathy was characterized by the colocalization of myocardial degeneration, the development of subepicardial, perivascular, subendocardial, and interstitial fibrosis, and mononuclear inflammatory cell infiltration that increased by incidence and severity in an age-dependent manner from 1 to 2 years. SD rats fed the 5002 diet AL had the greatest heart weights and the most severe cardiomyopathy, with the highest myocardial fibrotic index. These parameters were relatively decreased in the AL 5002-9 diet, the DR 5002 diet, and the DR 5002-9 diet rats at 1 and 2 years. Regardless of the type of diet fed, both AL groups had the most severe cardiomyopathy by 2 years. Moderate DR allowed isocaloric comparisons of the relative effects of modified diets on survival, obesity, and heart disease. Only slight improvements in the severity and progression of spontaneous cardiomyopathy were seen by modification of the protein, fiber, fat, and energy content of the diet if fed AL. However, moderate DR with either diet was more effective than changing the diet composition in preventing and controlling the progression of cardiomyopathy in male SD rats.

Aging↗

PubMed1990

Effects of interactions between photostimulation, dietary restriction and dietary maize oil dilution on plasma LH and ovarian and oviduct weights in broiler breeder females during rearing.

1. The response of the reproductive system to photostimulation was investigated during the rearing period in dwarf broiler breeder females maintained from hatch on 8 h light/d. The effect of increased body fat on this response was investigated. Body fat was increased by diluting the diet with maize oil. 2. A significant increase in plasma luteinising hormone (LH) was observed 4 d after photostimulation with 20 h light/d at 3 and 15 weeks of age in birds fed the restricted diet alone and at 3, 7, 11, 15 and 19 weeks of age in birds fed the restricted diet diluted with maize oil. 3. Increases in ovarian weight were observed two weeks after photostimulation at 15 weeks of age in birds fed the restricted diet alone and at 7, 11 and 15 weeks of age in birds fed the restricted diet diluted with maize oil. Increases in oviduct weight were seen after photostimulation at 11, 15 and 19 weeks of age in both dietary treatment groups; however, a larger increase in oviduct weight was seen at 15 and 19 weeks of age in birds fed the restricted diet diluted with maize oil. 4. In a second experiment, the dilution of a diet fed ad libitum with maize oil significantly increased body fat content and the baseline concentration of LH but did not enhance the response of the reproductive system to photostimulation. 5. Baseline plasma LH concentrations were lower in birds fed ad libitum than in those fed a restricted diet. 6. It is concluded that the neuroendocrine pathways involved in the transmission of photoperiodic information are functional at 3 weeks of age. The function of the components of the hypothalamo-pituitary complex which control reproductive activity is enhanced when a restricted diet diluted with maize oil is fed.

Animals↗

PubMedDate not supplied

Effect of dietary restriction on the response of alpha 2-macroglobulin during an acute phase response.

The effects of aseptic abscesses induced by subcutaneous injections of turpentine (5 mL/kg body weight) on the acute-phase protein response (alpha 2-macroglobulin, alpha 2-M) and on the circulating albumin and total protein concentrations were assessed in young rats that were made malnourished by restricting dietary intake to an extent that either impaired growth (60% of normal intake) or caused weight loss (0% to 45% of normal intake). The measurements were obtained daily during a period of 4 days in malnourished rats that had lost about 25% body weight but had maintained a stable weight thereafter, or in rats that had lost about 12% body weight and were continuing to lose weight at various rates at the time of the turpentine injection. In animals that were injected while they maintained a stable weight after losing about 25% body weight, the alpha 2-M response was attenuated fourfold to eightfold compared with control animals (the area under the 4-day alpha 2-M curve in control rats was 23.3 +/- 2.3 g/L/d). In the depleted animals that were injected while they were actively losing weight (approximately 12.5% weight loss), the attenuation of the alpha 2-M response was related to the rate of weight loss or to the extent of dietary restriction (area under the 4-day alpha 2-M curve ranged from 5.7 +/- 1.4 g/L/d in animals receiving 15% restricted diet to 15.6 +/- 1.5 g/L/d in animals receiving the 45% restricted diet).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗

PubMed1990

Modulation of free radicals and superoxide dismutases by age and dietary restriction.

Reducing dietary intake has been shown to be the most effective means for modulating aging processes in laboratory rodents. Dietary restriction has also been shown to be a modulator of membrane lipid peroxidation and cytosolic antioxidant status. In the present study, anti-radical action of dietary restriction was investigated further by quantitating the formation of the superoxide radical, hydroxyl radical and hydrogen peroxide by liver microsomes from rats of various ages. The results show that the ad libitum fed group maintained a higher production of superoxide and hydroxyl radicals when compared to the food restricted group of the same age. Hydrogen peroxide formation followed the same trend but was statistically greater only at 3 and 6 months of age. The food restricted group tended to show a higher superoxide dismutase (SOD) activity in both cytosolic and mitochondrial fractions than ad libitum fed controls. These data indicate that the free radical activity observed in the liver microsomes of ad libitum fed rats can be attenuated by dietary restriction, thereby providing a possible biochemical mechanism for its anti-lipoxidative action on membrane lipid peroxidation as reported in an earlier study. This action may in part underlie the life span-prolonging action of food restriction.

Aging↗

PubMedDate not supplied

FDA points-to-consider documents: the need for dietary control for the reduction of experimental variability within animal assays and the use of dietary restriction to achieve dietary control.

Standard protocols for conducting chronic toxicity and carcinogenicity studies have been refined over the years to carefully control for many variables. Nevertheless, over the last 2 decades, there has been a steady increase in variability, a decrease in survival, an increase in tumor incidence rates, and an increase in the average body weight of control animals among the various rodent species and strains used for toxicity testing. These observations have prompted an evaluation of chronic study designs to determine what factor(s) may be responsible for such confounding changes. Ad libitum feeding and the selection of successful breeders with rapid offspring growth is believed to be at least partially responsible for the heavier, obese rodents with which many laboratories are coping today. As a result of these changes, some studies used for the evaluation of safety have been deemed inconclusive or inadequate for regulatory purposes and either additional supportive studies have been requested and/or studies per se have been repeated. Research on the molecular mechanisms of caloric restriction and agent-induced toxicity at the Food and Drug Administration (FDA) National Center for Toxicological Research stimulated the first international conference on the biological effects of dietary restriction in 1989; this was followed in 1993 by an FDA workshop exploring the utility of dietary restriction in controlling reduced survival in chronic tests and an international conference in 1994 exploring the implications for the regulatory community of using dietary restriction in toxicity and carcinogenicity studies used in support of a sponsor's submission or in risk assessments. The outcome of that conference was the FDA's commitment to develop Points-to-Consider documents that address the issue of dietary control in chronic toxicity and carcinogenicity studies.

Animal Feed↗

PubMed1997

Reciprocal regional changes in brain NPY receptor density during dietary restriction and dietary-induced obesity in the rat.

Neuropeptide Y (NPY) potently induces feeding, reduces thermogenesis and induces obesity in rats when injected into the cerebral ventricles. Groups of male Wistar rats were either restricted to 60% of their normal daily food intake over 10 days or made obese by presenting them with a high-calorie diet rich in sugars and fat over 6 weeks. Food restricted rats lost up to 20% of their body weight, compared with control rats and had large reductions in their body fat mass. By contrast, rats with dietary-induced obesity weighed 26% more than controls due mainly to increased body fat mass. Quantitative receptor autoradiography demonstrated reduced [(125)I]PYY binding in the hypothalamic lateral (perifornical) and dorsal areas, hypothalamic ventromedial, arcuate and dorsomedial nuclei, hippocampal CA3 region, centromedial amygdaloid nucleus and thalamic paraventricular and reuniens nuclei in dietary restricted rats compared with controls. By contrast, regional [(125)I]PYY binding was significantly increased in hypothalamic lateral and dorsal areas, hypothalamic arcuate and dorsomedial nuclei, amygdaloid medial and centromedial nuclei, thalamic centromedial and paraventricular nuclei of dietary obese rats versus controls. Masking NPY Y1 receptors with 1 microM BIBP3226, a selective Y1 receptor antagonist, revealed that the changes in [(125)I]PYY binding in brains of food-restricted and dietary-obese rats were due to changes in BIBP3226-insensitive binding sites, presumably Y2 or Y5 NPY receptors. These data suggest that dietary-restriction stimulates NPY release resulting in down-regulation of NPY Y5 'feeding' and/or Y2 receptors and reduced BAT thermogenesis thereby providing an increased drive to eat to restore normal caloric intake whilst reducing thermogenesis in order to conserve fat reserves. By contrast, the up-regulation of NPY Y5 and/or Y2 receptors in dietary-induced obesity is consistent with inhibition of NPY release in the hypothalamus, amygdala and thalamus. Overall, we suggest that there is a regional increase in NPY release during negative energy balance, such as during food-restriction and a reduced regional release of NPY in positive energy balance, such as during hyperphagia associated with the development of obesity.

Amygdala↗

PubMed1988

Maternal dietary restriction causes myelin and lipid deficits in the brain of offspring.

The relationship between brain myelination and nutritional insufficiency in suckling rats whose dams had a restricted dietary intake was studied. The undernourished pups were characterized by body weight and brain weight that were 40-70% and 82-88% that of controls throughout the suckling period. Myelin concentrations, whether expressed as mg protein or as mg myelin dry weight per g wet brain, were 30-40% of normally fed controls. Myelin of undernourished rats contained total lipid, cholesterol, phospholipids, and sphingolipids that were 42, 54, 39, and 48%, respectively of the control counterparts. There was no change in the mole ratio of cholesterol:phospholipids:sphingolipids (i.e., cerebroside + sulfatide) in myelin from undernourished rats. Concentrations of individual phospholipids and sphingolipids were lowered by approximately the same percentage. Despite long-lasting, irreversible stunting of whole-body and brain growth, concentrations of myelin and myelin lipids returned to control levels after nutritional rehabilitation. Since the observed effects are different from those of more commonly used models, the present form of undernutrition may offer a useful system for studying the relationship between myelin lipids and brain development.

Animal Nutritional Physiological Phenomena↗

PubMed2005

A randomized single-blind trial of split-dose PEG-electrolyte solution without dietary restriction compared with whole dose PEG-electrolyte solution with dietary restriction for colonoscopy preparation.

BACKGROUND: Colonoscopy preparation regimens are poorly tolerated, requiring the use of a large volume of an unpalatable solution and diet restriction for adequate cleansing. The aim of this study was to compare the efficacy of two regimens of bowel preparation before colonoscopy: a whole dose of polyethylene glycol electrolyte solution (PEG-E), with diet restriction vs. a split dose with no diet restriction. METHODS: A total of 141 patients (ages 20-84 years, 81 men) were randomly assigned to receive either 4 L PEG-E, along with a liquid diet the day before colonoscopy (Group A) or 2 L PEG-E with a regular diet the day before colonoscopy followed by another 2 L PEG-E on the day of the procedure (Group B). The quality of the preparation was graded by the endoscopist (poor to excellent), who was blinded to the type of preparation. Tolerability of the assigned preparation and adverse effects were recorded by an independent investigator by using a questionnaire administered before colonoscopy. Intra- and interobserver variability was studied by using randomly chosen videotapes of colonoscopies performed as part of the study. RESULTS: There were 73 patients in Group A and 68 patients in Group B. The quality of the preparation was significantly better in Group B ( p = 0.011). The tolerability of the preparation regimen was not different overall between study groups in terms of side effects (except for bloating, which was more frequent in Group B, p = 0.039) or willingness to repeat the preparation. There was a nonsignificant trend toward improved adherence to the assigned preparation in favor of Group B ( p = 0.062). Inter- and intraobserver variability analysis showed good to excellent correlation among endoscopists. CONCLUSIONS: Colonic preparation with split-dose PEG-E and no dietary restriction provides better quality colon cleansing than whole-dose preparation, with no significant impact on patient tolerability and side effects.

Adult↗

PubMed2004

Dietary restriction and immune function.

Dietary restriction is beneficial in preventing a multitude of diseases, many of which may involve the immune system in their etiology. Recent reports examining dietary restriction focused on T lymphocytes and macrophages. Dietary restriction delays the onset of T-lymphocyte-dependent autoimmune disease; this may be attributed to improved antioxidant defense mechanisms, blunting shifts in T-lymphocyte subset proportions and preventing DNA mutation frequencies. The beneficial effects of dietary restriction were shown in both the CD4 and CD8 T-lymphocyte subsets as well as in various immune compartments such as the spleen, mesenteric lymph nodes, peripheral blood, thymus, and salivary glands. In contrast, dietary restriction may have negative effects on macrophage function because recent evidence showed that dietary restriction rendered mice more susceptible to peritonitis and stimulated macrophages produced lower amounts of cytokines. The application of dietary restriction regimens to humans would be difficult; however, understanding the biochemical and molecular targets of dietary restriction in the immune system may lead to the development of new dietary strategies to delay or prevent the onset of aging, cancer, and autoimmune disease.

Aging↗