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Results for “Caloric Restriction”

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At least 379 records · Page 21Linked to original sources

PubMed2005

Caloric restriction augments ROS defense in S. cerevisiae, by a Sir2p independent mechanism.

Aging is associated with increased production of reactive oxygen species (ROS) and oxidation-induced damage to intracellular structures and membranes. Caloric restriction (CR) has been demonstrated to delay aging in a variety of species. Although the mechanisms of CR remain to be clearly elucidated, reductions in oxidative damage have been shown to increase lifespan in several model systems. Contrary to the general belief that ROS production is reduced in CR, this article provides evidence that not only oxygen consumption but ROS production is enhanced in the calorie restricted condition. To understand the biological mechanism underlying the anti aging action of CR, the role of scavenging enzymes was studied. It was found that super oxide dismutase (SOD1 and SOD2), catalase and glutathione peroxidase (GPx) all are over expressed in CR. We further investigated the role of Sir2, a potential effector of CR response in the activation of scavenging enzymes. No marked difference was found in CR mediated activation of SOD and catalase in the absence of Sir2. Our results suggest that in CR scavenging enzymes are activated by a Sir2 independent manner.

Caloric Restriction↗

PubMed2003

Caloric restriction retards age-related changes in rat retina.

The neural retina of mammals consists of light sensitive photoreceptors and connecting neural cells that receive and send visual signal to the brain. Dietary caloric restriction (CR) is the only experimental intervention that can reliably retard the age-related degeneration of the retina in a normal mammalian model. Here, we studied the effect of CR on various biochemical parameters in the retina of male Brown Norway rats at different ages. We found that CR slowed the age-dependent protein insolubilization, blunted the declines in the total soluble thiols, and reduced glutathione and ascorbic acid levels in neural retina. We also observed that CR retarded the age-related decline in the levels of taurine, a vital amino acid in neural retina. These data are the first to implicate that CR may retard the age-related degeneration of retina by attenuating the oxidative stress and/or by sustaining the pool of protective factors in the neural retina.

Aging↗

PubMed2005

Effects of caloric restriction and gender on rat serum paraoxonase 1 activity.

Paraoxonase 1 (PON1) associates to specific high-density lipoproteins (HDLs)--those containing apolipoprotein A-I (apoA-I) and apolipoprotein J (apoJ)--and is largely responsible for their antiatherogenic properties. Caloric restriction (CR) has been shown to reduce major atherosclerotic risk factors. The aims of this work were to study PON1 activity response to CR (40% over 14 weeks) and to elucidate whether there are adaptive differences related to gender. Serum and liver paraoxonase and arylesterase activities, serum triglyceride, total and HDL cholesterol concentrations, serum PON1, apoA-I and apoJ contents and liver PON1 mRNA levels were measured. No effects of CR or gender were observed in triglyceride, total cholesterol concentration and PON1 mRNA levels. HDL cholesterol was higher in female rats than in male rats and increased with CR only in the latter animals. Serum PON1 activities tended to be higher in female rats and dropped with CR, with females showing the biggest decrease. Serum PON1 content was higher in female rats and decreased in both genders with CR, whereas apoA-I and apoJ contents, which were higher in female rats too, decreased only in the former animals, accounting for the high PON1 activity decrease observed in these animals. In conclusion, the short-term CR-associated reduction of serum PON1 activity and PON1, apoA-I and apoJ levels points toward a reduced stability of HDL-PON1 complexes and/or HDL particle levels responsible for PON1 transport and function in the blood. Moreover, the variations in PON1 activity and apolipoprotein levels show gender-related differences that are indicative of a different adaptive strategy of male and female rats when faced with a period of food restriction.

Animals↗

PubMed2004

Unchanged fasting and postprandial adiponectin levels following a 4-day caloric restriction in young healthy men.

OBJECTIVE: Adiponectin is an adipocyte-secreted protein that has been shown to promote fat oxidation and insulin sensitivity in animals. Whether acute energy restriction is associated with modulation of adiponectin in humans remains largely unknown. The purpose of this study was to examine the effects of a short-term caloric restriction on fasting and postprandial adiponectin levels in young healthy men. RESEARCH DESIGN AND METHODS: Fifteen young healthy men were subjected to a 4-day energy restricted diet (-800 kcal/day). Before and after the intervention, anthropometric measurements, fasting and postprandial glucose, insulin and adiponectin were measured at 0, 30 and 60 min after a fixed breakfast. RESULTS: While fat mass remained stable, minor but significant changes in weight were observed after the 4-day energy-restricted diet. Glucose and insulin levels increased postprandially, and patterns did not differ before and after the intervention. Fasting levels of adiponectin remained unchanged after the energy restriction, and postprandial levels were not significantly different from fasting levels either before, or after, the intervention. CONCLUSIONS: Fasting and postprandial adiponectin levels are not acutely modulated by a short-term energy restriction in young healthy men.

Adiponectin↗

PubMed2005

Caloric restriction and physical activity in zebrafish (Danio rerio).

Understanding the mechanism of energy flux may be critical for explaining how obesity has emerged as a public health epidemic. It is known that changes in caloric intake predictably alter physical activity levels (PA) in mammals. Here, our goal was to test the hypothesis that fasting induces a biphasic pattern of change in PA by measuring PA before and after long-term food deprivation in zebrafish. Compared to control-fed fish, food-deprived fish showed a significant increase in PA levels during the first 2 days of food deprivation. Subsequently, however, fasted fish showed a significant chronic decrease in PA compared to fish fed at weight-maintenance levels. These data are comparable to those seen with mammals, which also show a biphasic response of PA to caloric restriction. In a separate group of fish, long-term food deprivation, associated with decreases in PA, induced a significant increase in brain preproorexin mRNA levels compared to fed controls. No change in orexin mRNA was seen after 2 days of food deprivation. The finding that orexin mRNA expression is altered only after long-term starvation suggests that orexin may be coupled with the changes in PA seen at this time. Thus, the association between negative energy balance and reductions in PA occurs across genera in biology and is associated with predictable neurological changes in brain gene expression.

Animals↗

PubMed2003

Life span extension by reduction of the growth hormone-insulin-like growth factor-1 axis: relation to caloric restriction.

A reduced growth hormone (GH)-insulin-like growth factor (IGF)-1 axis is associated with an extension of lifespan in laboratory rodents. Several phenotypes of such animal models resemble those induced by caloric restriction (CR). Using a transgenic male Wistar rat model whose GH-IGF-1 axis was moderately suppressed by overexpression of the antisense GH transgene (tg), we elucidated a relationship between the effects of a reduced GH-IGF-1 axis and CR for some biomarkers of aging, lifespan, and pathologies. Heterozygous (tg/-) rats fed ad libitum (AL) had a dwarf phenotype similar to that of control nontransgenic (-/-) rats subjected to 30% CR from 6 wk of age. Both the reduced GH-IGF-1 axis and CR extended lifespan to a similar extent, although the effect of CR seemed to be greater. There was an additive effect of CR to lifespan extension when tg/- rats were subjected to CR. Pathologic analyses indicated that the preventive effect of CR on selected diseases was greater than that of the reduced GH-IGF-1 axis. The present study suggests that CR affects aging and longevity by mechanisms other than suppression of the GH-IGF-1 axis, although CR might exhibit its effects partly through the reduced GH-IGF-1 axis.

Adenoma↗

PubMed2005

Short-term caloric restriction does not modify the in vivo insulin signaling pathway leading to Akt activation in skeletal muscle of Ames dwarf (Prop1(df)/Prop1(df)) mice.

The purpose of this study was to analyze the interaction between caloric restriction (CR) and the dwarf mutation at the level of insulin sensitivity and signal transduction. To this end, we analyzed the in vivo status of the insulin signaling system in skeletal muscle from Ames dwarf (df/df) and normal mice fed ad libitum or subjected to short-term (20-day) CR. We measured insulin-stimulated phosphorylation of the IR and IRS-1, IRS-1-p85 association and Akt activation, and the abundance of the IR, IRS-1, p85, GLUT-4 and IGF-1 receptor in skeletal muscle. In terms of glucose homeostasis, the response to CR was different in both groups of animals. In normal animals, CR induced a significant reduction in both circulating insulin and glucose levels, while CR did not modify these parameters in df/df mice. We did not find any significant alteration in either activation or abundance of signaling molecules analyzed after short-term CR in either normal or Ames dwarf mice. We conclude that the initial adaptation to CR in normal mice is an increase in insulin sensitivity without changes in insulin signal transduction, and that this adaptation is not evidenced in df/df mice, probably since they are already hypersensitive to insulin.

Animals↗

PubMed2005

Short-term caloric restriction improves ischemic tolerance independent of opening of ATP-sensitive K+ channels in both young and aged hearts.

Ischemic tolerance decreases with aging and the cardioprotective effect of ischemic preconditioning (IPC) is impaired in aged animals. Although lifelong caloric restriction (CR) profoundly affects the physiological and pathophysiological modifications induced by aging and markedly increases life span in several species, it is unclear whether short-term CR affects ischemic tolerance and IPC in aged hearts. Six-month-old (Y) and 24-month-old (O) Fischer 344 male rats were randomly divided into two groups; AL rats were fed ad libitum, whereas CR rats were fed 90% of the caloric intake of AL for 2 weeks followed by 65% of the caloric intake for 2 weeks. Isolated perfused hearts were subjected to 25 min of ischemia followed by 30 min of reperfusion with or without IPC. The recovery of LV function after reperfusion improved with IPC in ALY but not in ALO. CR improved the recovery of LV function in both CRY and CRO but the cardioprotective effect of IPC was not additive to that of CR. Neither 5-hydroxydecanoate nor glibenclamide abrogated the protective effect of CR in either CRY or CRO. The recovery of myocardial high-energy phosphates after reperfusion was better with CR in both generations. There was no difference in myocardial expression levels of AMP-activated kinase (AMPK) but AMPK-alpha phosphorylated at Thr172 increased with CR in both Y and O. In conclusion, short-term CR improves myocardial ischemic tolerance independent of the opening of KATP channels in both Y and O. CR-induced cardioprotection is associated with an increase in activated AMPK.

AMP-Activated Protein Kinases↗

PubMed2001

Microarray profiling of gene expression in aging and its alteration by caloric restriction in mice.

An active research area in biological gerontology concerns the mechanisms by which caloric restriction (CR) retards the aging process in laboratory rodents. We used high density oligonucleotide arrays representing 6347 genes to determine the gene expression profile of the aging process in gastrocnemius muscle of male C57BL/6 mice. Aging resulted in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes. Most alterations were completely or partially prevented by CR. Transcriptional patterns of muscle from calorie-restricted animals suggest that CR retards the aging process by causing a metabolic shift toward increased protein turnover and decreased macromolecular damage. The use of high density oligonucleotide microarrays provides a new tool to measure biological age on a tissue-specific basis and to evaluate at the molecular level the efficacy of nutritional interventions designed to retard the aging process.

Aging↗

PubMed2002

Weight-cycling decreases incidence and increases latency of mammary tumors to a greater extent than does chronic caloric restriction in mouse mammary tumor virus-transforming growth factor-alpha female mice.

Multiple periods of caloric restriction (or fasting)/refeeding in rodents have had inconsistent effects on mammary tumor (MT) development. In the present study, the consequence of intermittent caloric restriction/refeeding resulting in weight-cycling was evaluated using an oncogene-induced MT mouse model. Hybrid mouse MT virus-transforming growth factor alpha (MMTV-TGF-alpha)/Lep(+)Lep(ob) female mice were used. Ad libitum-fed mice (n = 30) were fed American Institute of Nutrition (AIN)-93M diet. Beginning at 10 weeks of age, weight-cycled mice (n = 30) were fed an AIN-93 modified diet (2-fold increase in protein, fat, vitamin, and mineral contents) at 50% of ad libitum for 3-week intervals followed by 3-week intervals of ad libitum feeding using AIN-93M diet. Pair-fed mice (n = 33), were fed a 2:1 mixture of AIN-93M:AIN-93 modified diets to match the caloric intake of weight-cycled mice for each 6-week age-matched caloric restriction/refeeding interval. Food intakes were determined daily and body weights weekly. Mice were euthanized when MTs exceeded 20 mm in length or at 80 weeks of age. Final body weights were similar, but cumulative food intake of ad libitum-fed mice was 21% greater than that of the other groups. Ad libitum-fed mice had a 77% MT incidence versus 3% for weight-cycled and 44% for pair-fed mice. MTs were detected earlier for ad libitum-fed mice, 64.1 weeks versus 73.5 weeks for pair-fed mice. The only MT in one weight-cycled mouse was excised at necropsy (80 weeks of age) and weighed only 0.063 g. Average MT weight for ad libitum-fed mice was 1.034 g and for pair-fed mice was 0.667 g. Intervals of caloric restriction/refeeding resulting in weight-cycling were protective against MT development in this mouse model. Future studies should address the application of this intervention to additional transgenic mice as well as other MT models.

Animals↗

PubMed2006

Effects of caloric restriction and exercise on age-related, chronic inflammation assessed by C-reactive protein and interleukin-6.

Chronic inflammation is associated with the aging process and numerous age-related pathologies. We evaluated the effects of age, caloric restriction (CR), and exercise on plasma C-reactive protein (CRP), interleukin-6, and total antioxidant capacity in Fisher 344 rats. The inflammatory markers were analyzed using enzyme-linked immunosorbent assays (ELISA), while total antioxidant potential was determined by a spectrophotometric method. An increase in circulating levels of CRP with age was attenuated with long-term 40% CR; short-term 40% CR in young animals also reduced CRP concentration compared to age-matched controls. Lifelong exercise with 8% CR showed a marked decrease in CRP levels compared to 8% CR controls and an even greater reduction compared to ad libitum-fed rats. Plasma interleukin-6 levels remained unchanged with age, CR, and exercise, whereas inflammation levels showed an inverse association with plasma antioxidant status. These studies highlight the anti-inflammatory effects of CR and exercise.

Aging↗

PubMed2004

Measurement of the 4,834-bp mitochondrial DNA deletion level in aging rat liver and brain subjected or not to caloric restriction diet.

Several studies have demonstrated an age-related accumulation of the amount of a specific 4834-bp mitochondrial DNA (mtDNA) deletion in different tissues of rat (liver, brain, and skeletal muscle). We investigated the influence of a caloric restriction diet (CR) on a selected age-associated marker of mtDNA damage, as the 4834-bp deletion, using quantitative real-time PCR. The mtDNA deleted level has been determined with respect to the mitochondrial D-loop level, using specific primers and TaqMan probes for each target. In liver we found an age-related increase of the deletion level (twofold) that was reversed and brought back to the adult level by a CR diet. On the contrary, in the brain the age-related increase of the deletion level (eightfold) was not affected by CR at all. The different effect of the CR on the deletion level in liver and brain might be a further element supporting the tissue-specificity of the aging process.

Aging↗

PubMed2006

Long-term treatment with N-acetylcysteine, but not caloric restriction, protects mesenchymal stem cells of aged rats against tumor necrosis factor-induced death.

The survival of mesenchymal stem cells (MSCs) to tumor necrosis factor alpha (TNFalpha) stimulation was evaluated after a long-term antioxidant treatment, or caloric restriction, in aged rats. MSCs were isolated from bone marrow of 30-month-old rats which orally received N-acetylcysteine in the last 18 months. The necrotic cell death-induced in vitro by TNFalpha, determined by trypan blue exclusion, was markedly attenuated in MSCs obtained from treated vs. control aged rats (percent mean+/-SEM: 10.9+/-2.17 vs. 17.8+/-0.53; p<0.05). Also, the proliferation rate of MSCs from control, but not N-acetylcysteine-treated, aged rats evaluated up to 2 weeks was significantly higher than that of MSCs from younger (4-month-old) rats. No significant effect was observed relative to the parameters investigated when the aged rats were previously subjected to a hypocaloric diet for 18 months. In conclusion, a prolonged supplementation with N-acetylcysteine in rats can increase resistance to necrotic death of MSCs and may also counteract an excessive rate of MSC proliferation.

Acetylcysteine↗

PubMedDate not supplied

Effects of long-term caloric restriction on glucose homeostasis and on the first steps of the insulin signaling system in skeletal muscle of normal and Ames dwarf (Prop1df/Prop1df) mice.

Ames dwarf mice are a model of retarded aging and extended longevity and display enhanced insulin sensitivity. Caloric restriction (CR) and the dwarf mutation have additive effects on lifespan. To begin to understand the mechanisms behind this effect, an analysis of the in vivo status of the insulin signaling system was performed in skeletal muscle from Ames dwarf (df/df) and normal mice fed ad libitum or subjected to long-term (over 1 year) CR. The response to CR was different in both groups of animals. In normal animals, CR induced a significant reduction in both circulating insulin and glucose levels, together with an increase in the in vivo insulin-stimulated phosphorylation of the IR, a trend towards an increase in the in vivo insulin-stimulated phosphorylation levels of IR substrate-1, and an increase in the abundance of GLUT4 in muscle. In contrast, CR did not modify none of these parameters in df/df mice. Interestingly, CR induced a reduction in the p85 subunit of phosphatidylinositol 3-kinase abundance in skeletal muscle in both groups of animals. These results suggest that in skeletal muscle, long-term CR induces different effects on the first steps of the insulin signaling system in normal mice than in df/df mice.

Aging↗

PubMed2007

Caloric restrictions affect some factors involved in age-related hypercholesterolemia.

Ageing has been defined as a progressive decrease in physiological capacity and a reduced ability to respond to environmental stresses. It has been observed that diet-restricted animals show a minor morbidity in age-related disease. Among these age-related diseases, hypercholesterolemia is the most recurring one and it is often associated with cardiac failure. Several studies have been published indicating age-dependent changes in circulating levels of cholesterol in both humans and in rodents; recently changes have also been reported in the proteins involved in cholesterol homeostasis, that is, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), Insig-induced gene (Insig) protein, SREBP cleavage activating protein (SCAP), sterol regulatory element binding protein (SREBP), and low density lipoprotein receptor (LDLr). Most age-related modifications of biochemical parameters are normalized or very improved in food-restricted animals, so the aim of this work is to examine whether or not alterations of the factors involved in cholesterol homeostasis which occur during ageing could be counteracted by caloric restriction (CR). The data show that the diet restrictions used attenuate the age-related effects on the factors involved in the synthesis and the degradation rate of HMG-CoAR; in spite of this, CRs have a good effect on the age-related hypercholesterolemia whose reduction seems to depend both on the correct membrane LDLr localization and on the proper restored HMG-CoAR activity.

Aging↗

PubMed2004

Caloric restriction modulates early events in insulin signaling in liver and skeletal muscle of rat.

Mutations that extend life span in C. elegans suggest that the insulin/IGF-1 signaling (IS) pathway may play a key role in retarding aging and extending life span by caloric restriction (CR). To evaluate this hypothesis, male rats were subjected to either AL (ad libitum) or CR (40% from AL) for 2 and 25 months, and then the effects of CR on the early events in the IS pathway in liver and muscle were assessed. The results indicated that aging was accompanied by a significant decline in insulin receptor tyrosine phosphorylation (pY-IR) upon insulin stimulation in both tissues, which was correlated with a significant increase in the activity of protein tyrosine phosphatase 1B (PTP-1B). However, these alterations with age were attenuated by 25CR. Parallel changes observed in liver mRNA of CR rats were upregulated insulin receptor (IR), IGF-1R and IRS-1, but increased expression of IR mRNA was dissociated with the IR protein in 25CR rats. The expression of liver mRNAs involved in lipid metabolism was also analyzed. In contrast to 25AL rats, the expression of mRNAs for PPARs (alpha, delta, and gamma) was significantly increased in 25CR rats. SREBP-1c and fatty acid synthase were reduced, and other genes were increased, including hormone-sensitive lipase and PGC-1 by CR. The data suggest that the normal function of insulin receptor in liver and muscle is required for successful aging. An altered expression of transcription of a number of genes involved in lipid metabolism may also contribute to modulation of the IS pathway by CR.

Aging↗

PubMed2002

A mathematical model that accounts for the effects of caloric restriction on body weight and longevity.

Several aspects of energy dynamics, such as energy expenditure and caloric intake, are known to affect the aging process. In this article we therefore model the aging process within a mathematical framework describing the energy dynamics of an organism. The resulting model comprises food intake, body growth and survival. The equation for the mortality rate accounts for food consumption and is suited to describe caloric restriction data. For non-growing animals, the expression for the mortality rate reduces to the well-known Gompertz equation. We successfully applied our model to growth and survival data on mice exposed to different food levels.

Animals↗

PubMed2005

Aging and caloric restriction: effects on Leydig cell steroidogenesis.

We have shown previously that testosterone concentration in the blood serum of Brown Norway rat becomes reduced with aging, and that this results from reduced testosterone production by individual Leydig cells. Herein we examine the effects of caloric restriction (CR), an intervention shown to delay or inhibit age-associated pathologic and biologic changes in a number of systems and organisms, on Leydig cell steroidogenic function. CR (40%) was initiated in 4 month-old Brown Norway rats, and continued through age 34 months. Serum testosterone concentration in the ad libitum (AL)-fed controls was reduced by 30% from 5 to 13 months, by another 67% through 25 months, and then was sustained through 34 months. For the CR rats, the serum testosterone level was reduced to 45% of AL controls by 5 months, only 6 weeks after the initiation of the CR regimen. There was no further reduction through 25 months, at which time serum testosterone concentration in CR animals was significantly higher than in AL controls. By age 28-34 months, there was no significant difference between the two diets. The weights of prostate and seminal vesicle, two biomarkers of serum androgen levels, were consistent with the changes in serum testosterone concentration in both AL and CR animals. The ability of isolated Leydig cells to produce testosterone in vitro also paralleled the age- and CR-related changes in serum testosterone concentration. CR resulted in a rapid, 36% reduction in testosterone production from control by age 5 months. In contrast to cells from the AL rats, there were no further decreases in testosterone production through age 25 months. Indeed, Leydig cells from the 25 month-old CR rats produced significantly greater amounts of testosterone than cells from the 25 month-old AL rats. These results indicate that short-term CR results in the suppression of Leydig cell function and in reduction in serum testosterone levels. The significantly higher concentrations of serum testosterone concentration, and increased Leydig cell testosterone production, elicited by CR in 25 month-old rats compared to AL controls suggest that long-term CR can transiently suppress the reductions in steroidogenesis that are characteristic of aging.

Aging↗