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Results for “Caloric Restriction”

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At least 415 records · Page 23Linked to original sources

PubMed2004

Stress and hunger alter the anorectic efficacy of fluoxetine in binge-eating rats with a history of caloric restriction.

OBJECTIVE: We examined the effect of fluoxetine to suppress binge eating in rats with a history of caloric restriction (CR) and the extent to which this effect was altered by stress and hunger. METHOD: To detect heightened sensitivity to fluoxetine, young female rats were used to determine a subthreshold anorectic dose (2 mg/kg, intraperitonally). Another group of rats was either fed ad libitum or given multiple CR (to 90% body weight) and refeeding-to-satiety cycles. One half of the rats were then either spared or subjected to foot shock stress before fluoxetine treatment. RESULTS: A history of CR alone produced bingelike eating on palatable food (p < .001) and, although stress did not affect intake, it rendered CR rats hypersensitive to the satiety effect of fluoxetine. The feeding-suppression was mainly for chow (p < .05) and the effect was abolished if the rats were in negative energy balance. DISCUSSION: Results support the utility of this animal model to elucidate serotonergic changes linking dieting to binge eating. The diverse effects of fluoxetine on the type of food, and in hungry versus sated rats, suggest alternate brain mechanisms should be concomitantly targeted for improved treatment of binge eating disorders.

Animals↗

PubMed2001

Neuroendocrine and pharmacological manipulations to assess how caloric restriction increases life span.

As part of an effort to review current understanding of the mechanisms by which caloric restriction (CR) extends maximum life span, the authors of the present review were requested to develop a list of key issues concerning the potential role of neuroendocrine systems in mediating these effects. It has long been hypothesized that failure of specific neuroendocrine functions during aging leads to key age-related systemic and physiological failures, and more recently it has been postulated that physiological neuroendocrine responses to CR may increase life span. However, although the acute neuroendocrine responses to fasting have been well studied, it is not clear that these responses are necessarily identical to those observed in response to the chronic moderate (30% to 50% reduction) CR that increases maximum life span. Therefore the recommendations of this panel fall into two categories. First, further characterization of neuroendocrine responses to CR over the entire life span is needed. Second, rigorous interventional studies are needed to test the extent to which neuroendocrine responses to CR mediate the effects of CR on life span, or alternatively if CR protects the function of essential neuroendocrine cells whose impairment reduces life span. Complementary studies using rodent models, nonhuman primates, and humans will be essential to assess the generality of elucidated mechanisms, and to determine if such mechanisms might apply to humans.

Animals↗

PubMed2002

Gene expression patterns in calorically restricted mice: partial overlap with long-lived mutant mice.

To gain insight into the pathways by which caloric restriction (CR) slows aging, gene expression levels were assessed for each of 2,352 genes in the livers of 9-month-old CR and control mice. A total of 352 genes were found to be significantly increased or decreased by CR. The distribution of affected genes among functional classes was similar to the distribution of genes within the test set. Surprisingly, a disruption or knockout of the gene for the GH receptor (GHR-KO), which also produces life extension, had a much smaller effect on gene expression, with no more than 10 genes meeting the selection criterion. There was, however, an interaction between the GHR-KO mutation and the CR diet: the effects of CR on gene expression were significantly lower in GHR-KO mice than in control mice. Of the 352 genes altered significantly by CR, 29 had shown a significant and parallel alteration in expression in a previous study of liver gene expression that compared mice of the long-lived Snell dwarf stock (dw/dw) to controls. These 29 genes, altered both by CR and in dwarf mice, provide a list of biochemical features common to both models of delayed aging, and thus merit confirmation and more detailed study.

Animals↗

PubMed1975

Obesity and thyroid function. 2. The effect of prolonged caloric restriction on Achilles tendon reflex values.

The results obtained are indicative of changes in thyroid function during prolonged caloric restriction. Achilles tendon reflex values were studied in obese individuals under reducing treatment. More pronounced weight loss during the first three months was associated with a shortening of Achilles tendon reflex values, or its values remained unchanged. From the sixth month on a growing percentage of obese patients in our group displayed prolongation of Achilles tendon reflex values coupled with a decrease in weight showed a statistically significant prolongation of Achilles tendon reflex values. Thyreoglobulin given at this stage normalised Achilles tendon values and reinduced weight decrease.

Achilles Tendon↗

PubMed2002

Caloric restriction restores the cardioprotective effect of preconditioning in the rat heart.

Preconditioning (PC) describes the observation that brief periods of ischemia paradoxically protect the heart and limit necrosis caused by a subsequent more prolonged period of ischemia. However, the PC response is attenuated in hearts from 9- to 12-month-old Sprague-Dawley rats, as compared to young adults. This study determined whether long-term caloric restriction (CR) could preserve the PC response, since CR increases ischemic tolerance in these hearts. Following 6 months of CR, isolated hearts underwent PC followed by ischemia and reperfusion. In contrast to control hearts in which PC response was attenuated, PC in CR hearts was clearly of benefit. In these hearts, aortic flow was increased resulting in a dramatic improvement of cardiac output. Our study suggests that CR is effective in preserving the PC response.

Animals↗

PubMed2005

Macrosialin increases during normal brain aging are attenuated by caloric restriction.

During normal aging, microglia develop an activated phenotype characterized by morphologic changes and induction of CD11b, MHC II, and other inflammatory markers. We show that macrosialin (CD68), a macrophage-specific protein, is increased by aging in selected brain regions of male C57BL/6NNia mice. In corpus callosum and striatum, macrosialin mRNA and protein increased >or=50% (24 months versus 4 months); hippocampus and cerebellum were unchanged. Caloric restriction (CR) attenuated these age-related increases. Since CR attenuates age-related increases in oxidative damage and inflammation, we examined whether oxidized lipoproteins and inflammatory processes regulate macrosialin using murine BV-2 microglial cells as a model. Oxidized low-density lipoproteins (oxLDL) induced macrosialin protein by 50%. Moreover, macrosialin was induced in response to lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) which activates inflammatory pathways in BV-2 cells. Thus, the previously documented increase in oxidized lipoproteins, inflammation, and microglial activation during normal aging may contribute to the age-related increase in macrosialin expression.

Aging↗

PubMed1995

Caloric restriction and toxicity.

The modulatory effects of caloric intake on the rate and extent of both spontaneous and induced disease incidence is well known, but the significance of these effects in the interpretation of testing data has only recently become appreciated. This is especially true relative to the impact of caloric intake on both survival and background incidence for common tumors. In order to enhance the health and survival of animals ongoing chronic toxicity testing it has been suggested that such tests should restrict food consumption. Although this restriction will result in increasing survival of the test animals, it may also effect the expression of toxicity by altering agent metabolism and disease progression. Focus in this symposium is on the necessity to control dietary consumption in toxicity tests (dietary control), and if such a need does exist to what level of consumption should be diet be focused (caloric restriction).

Animals↗

PubMedDate not supplied

Effects of caloric restriction on insulin pathway gene expression in the skeletal muscle and liver of normal and long-lived GHR-KO mice.

Growth hormone receptor/binding protein knockout (GHR-KO) mice are characterized by resistance to growth hormone (GH), reduced insulin like growth factor 1 (IGF1) levels and enhanced insulin sensitivity and markedly increased lifespan. Findings in these and other long-lived mutant mice, and in normal animals subjected to caloric restriction (CR) indicate that insulin signaling is importantly involved in the control of longevity. We have examined the mRNA expression level of genes involved in insulin/IGF1 action in the skeletal muscle and liver of normal and GHR-KO mice fed ad libitum or subjected to long term 30% CR. The levels of IR, IRS1, IRS2, GLUT4 and IGF1 message in the skeletal muscle were reduced by CR in both normal and GHR-KO mice. In the liver, the results indicate that in GHR-KO mice mRNA expression of genes related to early steps of insulin signaling is up-regulated in the liver but not in the muscle. The results also show that improved insulin sensitivity in response to CR is not due to increased mRNA expression of the above genes in either normal or GHR-KO animals.

Animals↗

PubMed2004

Caloric restriction reverses the deficits in leptin receptor protein and leptin signaling capacity associated with diet-induced obesity: role of leptin in the regulation of hypothalamic long-form leptin receptor expression.

The objectives of this study were to determine if reduced long-form leptin receptor (ObRb) expression in diet-induced obese (DIO) animals is associated with deficits in maximal leptin signaling and, secondly, to establish the effects of short-term caloric restriction (CR) on ObRb expression and function. Groups of DIO and life-long chow-fed (CHOW) F344xBN male rats, aged 6 months, were given an i.c.v. injection containing 2 micro g leptin or artificial cerebrospinal fluid (ACSF) vehicle. Leptin induced a >6-fold increase in STAT3 phosphorylation in CHOW rats, but less than 2-fold increase in DIO. Reduced maximal leptin-stimulated STAT3 phosphorylation in DIO rats was coupled with a decline in both ObRb expression and protein. At this point, subgroups of DIO and CHOW animals underwent CR for 30 days and were then tested for acute leptin responsiveness. CR resulted in a 45 and 85% increase respectively in leptin-stimulated STAT3 phosphorylation in CHOW and DIO animals. Similarly, CR increased ObRb expression and protein in both CHOW and DIO animals. To explore the role of leptin in regulating ObRb expression, we reversibly overexpressed leptin in the hypothalamus and found that ObRb mRNA inversely follows central leptin expression. By enhancing both ObRb expression and signaling capacity, CR may enhance leptin responsiveness in leptin-resistant DIO animals.

Animals↗

PubMedDate not supplied

The glucocorticoid paradox of caloric restriction in slowing brain aging.

Glucocorticoids have a bimodal effect on cognition, hippocampal pyramidal neurons and long-term potentiation (LTP). Transient increases in glucocorticoids improve performance at spatial memory tasks and facilitate synaptic efficacy, depending on the context. On the other hand, long-term elevations of glucocorticoids are associated with decreased cognitive performance, attenuated synaptic efficacy and neuronal atrophy. Elevation of glucocorticoids during aging is also associated with mild cognitive impairment and hippocampal atrophy. Caloric restriction (CR), a dietary manipulation which extends life-span in rodents, also increases free plasma corticosterone. Recent data suggests that CR attenuates many brain aging changes and increases resistance of neurons to toxins and injury. Thus, a paradox may be considered: if CR causes chronic elevation of glucocorticoids, and if glucocorticoids can increase the risk of neurodegeneration, how can CR be neuroprotective. We suggest that the neuroprotective effects of CR outweigh the deleterious effects of glucocorticoids. The neuroprotective effects of CR that are discussed here include decreased plasma glucose, attenuated free radical generation, alterations of the vasculature, increased expression of heat shock proteins and neurotrophic factors, and attenuation of age-related glial activation.

Aged↗

PubMed1997

The physiologic, neurologic, and behavioral effects of caloric restriction related to aging, disease, and environmental factors.

Little is known about the mechanisms by which acute and chronic caloric restriction (CR) modulate disease, longevity, and toxicity. To study these endpoints, behavioral parameters such as food and water consumption and physiologic parameters such as motor activity, body temperature, metabolic output (oxygen use), and respiratory quotient (RQ) were continuously monitored in 26-month-old male B6C3F1 mice and Fischer 344 rats fed either ad libitum (AL) or a CR diet (60% of AL). Different dietary regimens were used: rodents were (1) chronically food-restricted using daily feeding starting at 14 months of age, (2) chronically food-restricted using alternate day feeding, or (3) abruptly switched from CR to AL (acute CR). The physiologic and behavioral changes seen with chronic and acute CR were consistent across strains and species. Average body temperature, the number of meals, and the ratio of food/water consumption were significantly lower in CR rodents than in AL rodents. Also, the daily range of body temperature, oxygen metabolism, RQ, average water consumption, and motor activity was significantly higher in CR rodents. CR caused the onset of altered neurobehavioral functions such as abnormal water consumption; increases in motor activity, serum corticosterone, and stress proteins (HSP); and decreases in the basal setpoint for body temperature and brain metabolism. These changes strongly suggest that many beneficial effects of CR are controlled by the hypothalamic-pituitary-adrenal axis via hormonal regulation. This study supports the assertion that nutritional status may be a primary factor of consideration in development of safety standards and assessment of risk.

Aging↗

PubMed1998

Influences of caloric restriction on age-associated skeletal muscle fiber characteristics and mitochondrial changes in rats and mice.

The effect of caloric restriction (CR) initiated in adult rats (17 months of age) on the abundance of deleted mitochondrial genomes, mitochondrial enzymatic abnormalities, and fiber number was examined in rat skeletal muscle. Vastus lateralis muscle from young (3-4 months) ad libitum-fed, old (30-32 months) restricted (35% and 50% CR, designated CR35 and CR50, respectively), and old ad libitum-fed rats (29 months) was studied. CR preserved fiber number and fiber-type composition in the CR50 rats. In the old rats from all groups, individual fibers were found with either no detectable cytochrome-c oxidase activity (COX-), hyperactive for succinate dehydrogenase activity (SDH++), or both COX- and SDH++. Muscle from the CR50 rats contained significantly fewer COX- and SDH++ fibers than did the muscle from the CR35 rats. CR50 rats also had significantly lower numbers of mtDNA deletion products in two (adductor longus and soleus) of the four muscles examined compared to CR35 rats. These data indicate that CR begun in late middle age can retard age-associated fiber loss and fiber-type changes as well as lower the number of skeletal muscle fibers exhibiting mitochondrial enzyme abnormalities. CR can also decrease the accumulation of deleted mitochondrial genomes.

Aging↗

PubMed1986

The effects of aerobic conditioning and/or caloric restriction in overweight men and women.

The purpose of this study was to compare the effects of exercise and/or caloric restriction for 12 wk on body composition, maximal aerobic power (VO2max), and serum lipids and lipoproteins in overweight individuals. Forty-eight males and 48 females (means age = 36.6 yr), 120-140% of ideal body weight, were randomly assigned to groups (N = 12 each) of diet-exercise (DE), diet (D), exercise (E), and sedentary control (C). The dietary regimen consisted of 1,200 kcal X d-1, while exercise consisted of 5 d X wk-1 of 30 min of walk/running. For the males, body weight (BW) and fat weight loss in the DE group (-11.8 and 23%, respectively) were significantly greater than in the D group (-9.1 and -18%), with both groups significantly greater than for E and C. In the females, BW and fat weight loss for DE (-10.4 and -24%) were significantly greater than for D (-7.8 and -20%), with both groups significantly greater than E and C. Both DE and D males and females had a decrease in fat-free weight of -4.5 and -2.4%, respectively. In both sexes, the increase in VO2max-BW (ml X kg -1 X min-1) in DE (25%) was significantly greater than for E (15%), D (11%), and C (0%), with differences between E and D nonsignificant. However, increases in absolute VO2max (1 X min-1) and VO2max-fat-free weight (ml X kg-1 X min-1) were similar (P greater than 0.05) for DE and E (14%) but significantly greater compared to D and C (2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗

PubMed2005

Accelerated aging pathology in ad libitum fed Xpd(TTD) mice is accompanied by features suggestive of caloric restriction.

Trichothiodystrophy (TTD) patients with a mutation in the XPD gene of nucleotide excision repair (NER) have a short life span and show various features of premature aging, thereby linking DNA damage to the aging process. Xpd(TTD) mutant mice share many features with TTD patients, including a shorter life span, accompanied by a segmental progeroid phenotype. Here we report new pathology features supportive to the premature aging phenotype of Xpd(TTD) mice. Strikingly, accelerated aging pathology is accompanied by signs suggestive of caloric restriction (CR), a condition usually linked to retardation of age-related pathology and life extension. Accelerated aging symptoms in Xpd(TTD) mice are most likely due to accumulation of endogenously generated DNA damage and compromised transcription leading to cell death, whereas CR symptoms may reflect the need of Xpd(TTD) mice to reduce metabolism (ROS production) in an attempt to extend their life span. Our current findings in Xpd(TTD) mice further strengthen the link between DNA damage, repair and aging.

Aging↗

PubMed2006

Caloric restriction and growth hormone receptor knockout: effects on expression of genes involved in insulin action in the heart.

Blockade of growth hormone (GH), decreased insulin-like growth factor-1 (IGF1) action and increased insulin sensitivity are associated with life extension and an apparent slowing of the aging process. We examined expression of genes involved in insulin action, IR, IRS1, IRS2, IGF1, IGF1R, GLUT4, PPARs and RXRs in the hearts of normal and GHR-/- (KO) mice fed ad libitum or subjected to 30% caloric restriction (CR). CR increased the cardiac expression of IR, IRS1, IGF1, IGF1R and GLUT4 in normal mice and IRS1, GLUT4, PPARalpha and PPARbeta/delta in GHR-KO animals. Expression of IR, IRS1, IRS2, IGF1, GLUT4, PPARgamma and PPARalpha did not differ between GHR-KO and normal mice. These unexpected results suggest that CR may lead to major modifications of insulin action in the heart, but high insulin sensitivity of GHR-KO mice is not associated with alterations in the levels of most of the examined molecules related to intracellular insulin signaling.

Aging↗

PubMed2005

Mice and flies and monkeys too: caloric restriction rejuvenates the aging immune system of non-human primates.

Humanity has been obsessed with extending life span and reversing the aging process throughout recorded history and this quest most likely preceded the invention of the written word. The search for eternal youth has spurred holy wars and precipitated the discovery of the new world (the 'Fountain of youth'). It therefore comes as no surprise that an increasingly greater amount of research effort is dedicated to improve our understanding of the aging process and finding interventions to moderate its impact on health. Caloric restriction (CR) is the only intervention in biology that consistently extends maximal and median life span in a variety of short-lived species. Several theories to explain the mechanisms of action of CR have been put forth, including the possibility that CR acts by retarding immune senescence. The question remains, however, whether CR will have the same beneficial impact on human aging, and, if so, how long does CR need to last to produce beneficial effects. To address this question, several groups initiated long-term studies in Rhesus macaques (RM) in the 1980s. Here, we review published data describing the impact of CR on the aging immune system of mice and primates, and discuss our unpublished data that delineate similarities and differences in the effects of CR upon T cell aging and homeostasis between these two models.

Aging↗

PubMed1998

The effect of high altitude and caloric restriction on reactive carbonyl derivatives and activity of glutamine synthetase in rat brain.

Both exposure to high altitude (HA) and caloric restriction (CR) may influence free radical generation. The aim of the present study was to evaluate the effects of 4 wk chronic exposure to 4,000m of HA and CR (60% of CR of control (C) rats) on protein oxidation in brain. Eighteen rats with similar body mass were assigned to CR, HA and C rats. Reactive carbonyl derivatives (RCD), marker of protein oxidation, were measured by Western blot. In addition, the activity and protein content of glutamine synthetase (GS) were determined. The body mass of C rats was significantly higher (P< 0.001) than that of HA and CR groups. The quantified signal intensity of RCD was significantly stronger in C rats than in HA and CR rats. The activity of GS was significantly increased in CR rats, while the protein content of GS was decreased in HA rats compared to C group. The data suggest that both HA and CR decreases the accumulation of RCD in the brain, however the mechanism of the decrease seems to be different during HA and CR.

Altitude↗

PubMedDate not supplied

Caloric restriction and insulin-like growth factors in aging and cancer.

This review examines the influence of a reduction in caloric intake on cancer and longevity. Data indicating that rodents subjected to caloric restriction display lower tumor incidence, reduced susceptibility to carcinogens and extended lifespan is analyzed. The potential role of the growth hormone/insulin-like growth factor type 1 (IGF-I) axis in this effect is discussed as is the evidence that a reduction in growth hormone and/or IGF-I leads to a reduction in spontaneous tumors and susceptibility to carcinogens.

Aging↗