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Results for “Caloric Restriction”

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PubMed1989

Caloric restriction perturbs the pituitary-ovarian axis and inhibits mouse mammary tumor virus production in a high-spontaneous-mammary-tumor-incidence mouse strain (C3H/SHN).

Dietary restriction (DR) retards aging and extends maximum life span. It is also known to decrease the incidence of hormone-dependent tumors. In the present investigation, we focussed primarily on the influence of DR on the pituitary-ovarian axis, and subsequently on gene expression of the mouse mammary tumor virus. F1 females from the mating of SHN female and C3H male mice were used in this study, since these hybrids display a very high incidence of mouse mammary tumors. The mice weaned at 3 weeks were raised on either a calorically-restricted diet (DR: 50 kcal/week; N = 5) or on a control diet (C: 95 kcal/week N = 5) for 5 weeks. Three C57BL/6J Jcl ad libitum-fed female mice, 8 weeks of age, were used as reference animals since this strain has a very low incidence of mammary tumors. The mean cellular contents of prolactin (PRL) and growth hormone (GH) in the pituitary, as determined by immunohistochemistry, were found to be reduced in mice raised on the DR diet. The decrease in the mean cellular content of PRL (50% of the mean control value) was accompanied by a decrease in the number of lactotrophs (17% of the mean value of control diet mice). However, the decrease in cellular content of GH (53% of the mean control value) was not accompanied by a decrease in the number of somatotrophs (no. of somatotrophs in DR = 103% of mean control value). Histologically, ovaries from DR mice showed many growing and atretic follicles, with few corpora lutea. In contrast, both control-diet and reference (C57BL/6J Jcl) mice showed two or three corpora lutea per ovarian section. In accordance with this finding, DR mice had not established stable estrus cycles by 8 weeks of age, in contrast to both control-diet and reference mice. Since caloric restriction has been shown to decrease mammary tumor virus (MMTV) gene expression, MMTV production was investigated by electron microscopy to confirm the validity of our experimental conditions. In DR or reference C57BL/6J Jcl mice, MMTV particles were rarely found in the mammary gland samples, but were always found in samples from control mice. The development of mammary glands, as indicated by the number of villi or the development of the rough endoplasmic reticulum, was delayed in DR mice. Thus, it was concluded that caloric restriction decreases the number of lactrotrophs, inhibits ovulation and delays mammary gland development. This immature status is considered to be due to perturbations in the pituitary-ovarian axis by caloric restriction.

Animals↗

PubMed2005

Energy expenditure of calorically restricted rats is higher than predicted from their altered body composition.

Debate exists over the impact of caloric restriction (CR) on the level of energy expenditure. At the whole animal level, CR decreases metabolic rates but in parallel body mass also declines. The question arises whether the reduction in metabolism is greater, smaller or not different from the expectation based on body mass change alone. Answers to this question depend on how metabolic rate is normalized and it has recently been suggested that this issue can only be resolved through detailed morphological investigation. Added to this issue is the problem of how appropriate the resting energy expenditure is to characterize metabolic events relating to aging phenomena. We measured the daily energy demands of young and old rats under ad libitum (AD) food intake or 40% CR, using the doubly labeled water (DLW) method and made detailed morphological examination of individuals, including 21 different body components. Whole body energy demands of CR rats were lower than AD rats, but the extent of this difference was much less than expected from the degree of caloric restriction, consistent with other studies using the DLW method on CR animals. Using multiple regression and multivariate data reduction methods we built two empirical predictive models of the association between daily energy demands and body composition using the ad lib animals. We then predicted the expected energy expenditures of the CR animals based on their altered morphology and compared these predictions to the observed daily energy demands. Independent of how we constructed the prediction, young and old rats under CR expended 30 and 50% more energy, respectively, than the prediction from their altered body composition. This effect is consistent with recent intra-specific observations of positive associations between energy metabolism and lifespan and theoretical ideas about mechanisms underpinning the relationship between oxygen consumption and reactive oxygen species production in mitochondria.

Animals↗

PubMed2001

Caloric restriction and cancer.

In 1909 Moreschi observed that tumors transplanted into underfed mice did not grow as well as those transplanted into mice fed ad libitum. His finding stimulated a decade of research which showed that caloric restriction also affected negatively the growth of spontaneous tumors. Between 1920 and 1940 little work was done in this area, possibly because of limiting methodology. In the 1940s the laboratories of Tannenbaum (Chicago) and Baumann (Wisconsin) were able to design studies using defined diets and showed that the observed effect was due to caloric content of the diet independently of the source of calories. After another active decade research activity in the calorie-cancer area declined until it was reborn in the 1980s. By the 1980s knowledge of physiology and molecular biology had advanced enough to allow investigators to probe mechanisms underlying the calorie-cancer phenomenon. We now know that caloric expenditure (as work or exercise) will lead to reduced risk. Energy restriction enhances DNA repair and moderates oxidative damage to DNA. Energy restriction reduces oncogene expression as well. Over a half century ago, Boutwell noted that energy restriction in female rats resulted in adrenal hypertrophy and reduced weight of ovaries and uterus. He suggested that energy restriction resulted in "pseudohypophysectomy." We now know that adrenalectomy can negate the effects of caloric restriction. Caloric restriction also affects insulin metabolism and may influence gene expression. These recent observations should help us understand some of the basic mechanisms involved in establishment and proliferation of tumors.

Animals↗

PubMed1996

Inhibitory effect of caloric restriction on tumorigenicity induced by 4-aminobiphenyl and 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) in the CD1 newborn mouse bioassay.

The tumorigenicity of 4-aminobiphenyl (4-ABP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were studied in combination with caloric restriction in the male neonatal CD1 mouse bioassay. 4-ABP and PhIP exhibited moderate and weak tumorigenicity, respectively, in ad libitum fed mice; however, none of the caloric restricted mice developed tumors. These results indicate that caloric restriction, even when begun 3 months after the conclusion of compound treatment, markedly inhibited 4-ABP- and PhIP-induced tumors in the CD1 mouse.

Aminobiphenyl Compounds↗

PubMed2006

Effects of caloric restriction and a moderate or intense physiotherapy program for treatment of lameness in overweight dogs with osteoarthritis.

OBJECTIVE: To evaluate the effects of a weight reduction program combined with a basic or more complex physical therapy program including transcutaneous electric nerve stimulation on lameness in overweight dogs with osteoarthritis. DESIGN: Nonblinded prospective randomized clinical trial. Animals-29 adult overweight or obese dogs with a body condition score of 4/5 or 5/5 and clinical and radiographic signs of osteoarthritis. PROCEDURES: A weight-loss program was initiated for all dogs. One group received caloric restriction and a home-based physical therapy program. The other group received the identical dietetic protocol and an intensive physical therapy program including transcutaneous electrical nerve stimulation. Lameness was assessed clinically and by kinetic gait analysis on a treadmill with 4 force plates to measure symmetry of ground reaction forces (GRFs) of the affected and contralateral limbs in bimonthly intervals for 6 months. RESULTS: Significant weight loss was achieved in both groups; however, greater weight reduction was attained by dogs treated with caloric restriction and intensive physiotherapy. Mobility and symmetry indices of GRFs were improved after 6 months; the best outcome was detected in the group receiving energy restriction combined with intensive physical therapy. CONCLUSIONS AND CLINICAL RELEVANCE: Caloric restriction combined with intensive physical therapy improved mobility and facilitated weight loss in overweight dogs. The combination of dietetic and physical therapy may help to improve the health status more efficiently than dietetic treatment alone.

Animals↗

PubMed1995

Strenuous exercise with caloric restriction: effect on luteinizing hormone secretion.

To test whether strenuous exercise with and without caloric restriction alters LH secretion, and whether these changes are apparent in the immediate post-exercise period, LH pulse parameters were studied in four moderately trained eumenorrheic women over three successive menstrual cycles. Blood samples were obtained 5 h before and 5 h after 90 min of running at 74% VO2max. Each test was preceded by a 7-d treatment of controlled diet and exercise (74% VO2max). During CONTROL, subjects were eucaloric on days 1-7, and performed no exercise on days 5-7. During STTI (short-term training increase), subjects were eucaloric and completed 90 min runs on days 5-7. During DIET/STTI, subjects consumed 60% of the calories necessary to maintain weight on days 1-7, and exercised as in STTI. A significant decrease in overall (0700-1830 h) LH pulse frequency during DIET/STTI compared with CONTROL and STTI treatments was observed. No changes were found in mean serum LH levels or peak amplitude. These results suggest that high-volume training combined with caloric restriction may predispose one to exercise-induced changes in LH pulse frequency, while adequate caloric intake may prevent these changes.

Adult↗

PubMed2005

Tumor necrosis factor alpha signaling in skeletal muscle: effects of age and caloric restriction.

Past the age of 50 years, aging individuals lose muscle mass at an approximate rate of 1-2% per year. This age-related muscle atrophy, termed sarcopenia, can have significant effects on individual health and quality of life and can also impact the socioeconomic status. Sarcopenia is due to both a decrease in the number of fibers and the atrophy of the remaining fibers. The mechanisms causing loss of fibers have not been clearly defined, but may likely involve apoptosis. Elevated levels of circulating tumor necrosis factor alpha (TNF-alpha) and adaptations in TNF-alpha signaling in aged skeletal muscle may be contributing factors for the activation of apoptosis. These adaptations may be fiber-type specific, which could explain the selective loss of type II fibers, vs. type I fibers, in the aging process. Caloric restriction, a proven antiaging intervention, is known to attenuate the loss of muscle mass and function with age. Furthermore, caloric restriction has been shown to attenuate the age-associated adaptations in TNF-alpha signaling in skeletal muscle, which may be a possible mechanism by which CR prevents apoptosis and the loss of muscle fibers with age. The potential role of TNF-alpha in the progression of sarcopenia will be discussed, as well as the effects of life-long caloric restriction on TNF-alpha signaling.

Aged↗

PubMed2006

Transient caloric restriction in early adulthood hastens disease endpoint in male, but not female, Cu/Zn-SOD mutant G93A mice.

Long-term caloric restriction (CR) prolongs the lifespan in healthy insects, rodents, and nonhuman primates. We previously reported that long-term CR improves motor performance but hastens clinical onset of disease in an animal model of amyotrophic lateral sclerosis (G93A mice). G93A mice overexpress the mutant human Cu/Zn-SOD gene and show progressive lower motor neuron weakness and increased oxidative stress. To study short-term (15 days) CR in the same animal model, we investigated the effect of transient caloric restriction (TCR) on paw grip endurance, clinical onset, disease progression (time from clinical onset to endpoint), and lifespan. Starting at age 40 days, 32 separately caged G93A mice were randomly divided into two groups: ad libitum (AL, n = 17; 10 females, 7 males) and TCR (n = 15; 6 females, 9 males) with a diet equal to 60% of AL. When the TCR mice lost 30% of their weight they were offered food AL until endpoint, otherwise all TCR mice were provided food AL from age 55 days until endpoint (i.e., range of TCR = 13-15 days). Paw grip endurance started to decrease significantly at age 96 days compared with baseline values for all the groups. TCR males reached clinical onset 5 days sooner than TCR females. Disease progression was 8 days faster in TCR mice than AL mice and 6 days faster in male mice than female mice. The probability of survival was significantly different between the groups, with the TCR males having a faster rate of reaching endpoint than TCR females, AL males, and AL females. We conclude that TCR hastens clinical onset of disease and shortens the lifespan in male, but not female, G93A mice. Moreover, TCR hastens progress of disease but has no effect on paw grip endurance. The female sex is protective against the detrimental effects of short-term CR in G93A mice. Assuming we can extrapolate these results to humans, short-term CR should be avoided in patients with amyotrophic lateral sclerosis, especially men.

Amyotrophic Lateral Sclerosis↗

PubMed2002

Effects of aging and caloric restriction on the gene expression of Foxo1, 3, and 4 (FKHR, FKHRL1, and AFX) in the rat skeletal muscles.

In C. elegans, insulin-like hormone signal pathway plays a significant role in longevity. In particular, daf-16 gene product is indispensable factor for this lifespan-extension. This signal pathway is critical for dauer formation, which is a similar state to hibernation in mammals. We examined the expression level of mammalian daf-16 homologues, Foxo 1,3, and 4 (FKHR, FKHRL1, and AFX) mRNAs in the rat skeletal muscles during aging and in 30% caloric restricted of ad libitum fed. The expression level of AFX mRNA was significantly higher at 6 and 12 months than at 3 and 26 months, and FKHRL1 expression was significantly higher at 6 months than at 3 and 26 months but FKHR expression showed no significant change with age. We observed a characteristic expression of AFX and FKHR mRNAs to be significantly higher in the second day in caloric restriction by every-other-day feeding than in ad libitum fed. This suggests that caloric restriction may increase the expression of FKHR-family genes and prevent the aging process in the skeletal muscles.

Aging↗

PubMed2004

Leydig cell gene expression: effects of age and caloric restriction.

In mammals, the concentration of testosterone in blood serum typically becomes reduced with aging. We have shown that, in rats, this results from reduced testosterone production by individual Leydig cells. To gain an understanding of the mechanisms by which Leydig cell steroidogenic function changes with aging, we compared the gene expression profiles in Leydig cells isolated from young and old Brown Norway rats, focusing on possible changes in genes involved in, or associated with, steroidogenesis. We also explored the effects of caloric restriction, an intervention shown to delay or inhibit age-associated pathologic and biologic changes in a number of systems and organisms, on the expression of these genes. Of the total of 1176 genes arrayed on each of the five membranes per group that we used, about 500 (45%) were detectable in Leydig cells isolated from young and old rat testes, with the same genes detectable in cells from both ages. An ANOVA model was applied to statistically analyze the 500 detectable genes in the four treatment groups. The primary criterion by which interesting genes were selected was a P value of </=0.05. With aging, a large number of genes were seen with fold changes of >1.5. However, when P</=0.05 was used as the selection criterion, only 45 genes were seen to change significantly with age. Most, but not all, of these genes also had fold changes of >1.5. Among the 500 genes, 17 were found to decrease in expression with aging, the most prominent among which were genes involved in steroidogenesis and stress response/free radical scavenging. Long-term caloric restriction had little effect on the 45 genes altered by age. In contrast to the effects of caloric restriction as seen in many other cell types and systems, the vast majority (44/45) of the Leydig cell genes that changed with age were not 'rescued' by this intervention.

Aging↗

PubMed1995

Interaction of hypertension and caloric restriction on cardiac mass and isomyosin expression.

Previous studies show that elevations in blood pressure induce concomitant increases in both cardiac mass and slow beta-myosin heavy chain (MHC) expression in rodents, whereas caloric restriction of 50% (CR) causes an increase in beta-MHC while modestly lowering blood pressure in normotensive rats. The goals of this study were to 1) determine if beta-MHC expression could be independently regulated by CR and hypertension when these two interventions are combined and 2) determine if CR exerts a lowering of blood pressure in two contrasting models of rodent hypertension. Rodents were assigned to the following groups: 1) normal control (NC); 2) abdominal aortic constriction (Abcon), a model that induces hypertension via renin-angiotensin II; 3) nephrectomy-deoxycorticosterone acetate treatment (DOCA), a model that induces hypertension through increased salt retention; 4) CR; 5) Abcon+CR; 6) DOCA+CR. Results show that both Abcon and DOCA induced significant increases in systemic blood pressures, left ventricular (LV) weight/body weight, and the relative content of beta-MHC compared with NC. When applied in combination with either Abcon or DOCA, CR significantly blunted the changes observed in both systemic blood pressures and LV weight/body weight. In contrast, CR in conjunction with DOCA augmented % beta-MHC expression relative to either DOCA or CR alone. These data suggest 1) caloric restriction exerts a powerful impact on reducing experimentally induced hypertension in rodents and 2) the regulation of beta-MHC expression appears to be regulated by at least two processes, one associated with the stimulus of hypertension and the other involving an independent pathway linked to caloric restriction.

Animals↗

PubMed1990

Effect of chronic caloric restriction on the synchronization of various physiological measures in old female Fischer 344 rats.

A variety of physiological and behavioral parameters which relate to metabolism were continuously monitored in 18 month old female Fischer 344 rats which were maintained on either ad libitum or reduced calorie diets. Caloric restriction (CR) stimulated average motor activity per day, the duration of each feeding episode, food consumed per episode, and water consumed per gram lean body mass (LBM). However, CR limited total food consumption, feeding time, number of feeding episodes per day, total eating and drinking time, and the daily ratio of food consumed to water consumed, CR also decreased average body temperature per day, O2 consumption, CO2 production, and respiratory quotient. A variety of parameters concerning water consumption were not affected. CR rats ate their food immediately when food was presented during the light span, while ad libitum fed animals ate numerous small meals throughout the entire dark span. An anticipatory response to restricted feeding was also noted. Total motor activity, metabolism, and body temperature increased just prior to scheduled feeding and reached maximum values shortly after feeding, suggesting that these parameters were highly synchronized to feeding. Females and males were found to respond to caloric restriction in a similar fashion. Dramatic changes in respiratory quotient and body temperature suggest rapid shifts between metabolic pathways (glycolysis to gluconeogenesis) to obtain optimal efficiency. Lower body temperature and metabolism may provide protection against DNA damage, thereby increasing the survival potential of restricted rats. These responses may provide insight into the mechanisms by which caloric restriction acts to extend life span.

Aging↗

PubMed2003

Regional fat pad growth and cellularity in obese zucker rats: modulation by caloric restriction.

OBJECTIVE: To investigate, in young obese male Zucker rats, the effects of chronic food restriction and subsequent refeeding on: 1). parameters of nonadipose and adipose growth, 2). regional adipose depot cellularity [fat cell volume (FCV) and number], and 3). circulating leptin levels. RESEARCH METHODS AND PROCEDURES: Obese (fa/fa) and lean (Fa/?) male Zucker rats were studied from age 5 to 19 weeks. After baseline food intake monitoring, 10 obese rats were subjected to 58 days of marked caloric restriction from ad libitum levels [obese-restricted (OR)], followed by a return to ad libitum feeding for 22 days. Ten lean control rats and 10 obese control rats were fed ad libitum for the entire experiment. All rats were fed using a computer-driven automated feeding system designed to mimic natural eating patterns. RESULTS: After food restriction, OR rats weighed significantly less than did lean and obese rats and showed a significant diminution in body and adipose growth as compared with obese rats. Relative adiposity was not different between obese and OR rats and was significantly higher than that of lean rats. The limitation in growth of the adipose tissue mass in OR rats was due mostly to suppression of fat cell proliferation because the mean FCV in each of the four depots was not affected. Serum leptin levels of OR and obese rats were not different from each other but were significantly higher than those of lean rats. DISCUSSION: Marked caloric restriction affects obese male Zucker rats in a manner different from that of nongenetic rodent models (i.e., Wistar rats). In comparison with the response to caloric deprivation of Wistar rats, these calorically restricted obese male Zucker rats appeared to defend their relative adiposity and mean FCV at the expense of fat cell number. These findings indicate that genetic and/or tissue-specific controls override the general consequences of food restriction in this genetic model of obesity.

Adipose Tissue↗

PubMed2000

Normal mouse and rat strains as models for age-related cataract and the effect of caloric restriction on its development.

The purpose of this study was to determine: (1) which of the commonly used strains of laboratory rats and mice provide good models for human age-related cataract, and (2) whether long term caloric restriction, a regimen that prolongs both median and maximum life span in rodents, would also delay the time of appearance of this age-related pathology. Three strains of mice and two rat strains commonly used in laboratory work and maintained on either ad libitum (AL) or calorically restricted (CR) diets in the National Institutes of Aging and Diet Restriction colony were examined by slit lamp for age-related cataracts at four or more time points during their life spans. These strains were Brown Norway and Fischer 344 rats, and C57BL/6, (C57BL6 x DBA/2)F1 and (C57BL/6 x C3H)F1 mice. None of these strains develop congenital cataracts. Various stages of cataract were found in the great majority of these animals in old age. In both rat strains and one mouse strain the cataracts occurred after mid-life, were most advanced late in life, and were similar in locations and appearance to those in humans. In the two mouse strains in which some cataracts appeared as early as 10-14 months of age, previously identified genetic defects affecting the eye were probably involved in the early appearances. CR extended life spain in all five rat and mouse strains and also delayed both the time of first appearances and the subsequent increase in cataract severity over time in the four dark-eyed strains. CR did not delay cataract formation in the single albino rat strain studied. In summation: (1) commonly used strains of laboratory rats and mice that are free of congenital or early appearing cataracts due to genetic defects would appear to serve as appropriate models for human age-related cataract, (2) caloric restriction (CR) provides a protective effect, delaying development of cataracts in the dark-eyed mouse and rat strains, while also extending their life spans, (3) CR did not delay the development of lens damage in the nonpigmented eye of the single albino strain studied, although it extended life span.

Aging↗

PubMed2000

Reversible effects of long-term caloric restriction on protein oxidative damage.

The age-associated increase in oxidative damage in ad libitum-fed mice is attenuated in mice fed calorically restricted (CR) diets. The objective of this study was to determine if this effect results from a slowing of age-related accumulation of oxidative damage, or from a reversible decrease of oxidative damage by caloric restriction. To address these possibilities, crossover studies were conducted in C57BL/6 mice aged 15 to 22 months that had been maintained, after 4 months of age, on ad libitum (AL) or a 60% of AL caloric regimen. One half of the mice in these groups were switched to the opposite regimen of caloric intake for periods up to 6 weeks, and protein oxidative damage (measured as carbonyl concentration and loss of sulfhydryl content) was measured in homogenates of brain and heart. In AL-fed mice, the protein carbonyl content increased with age, whereas the sulfhydryl content decreased. Old mice maintained continuously under CR had reduced levels of protein oxidative damage when compared with the old mice fed AL. The effects of chronic CR on the carbonyl content of the whole brain and the sulfhydryl content of the heart were fully reversible within 3-6 weeks following reinstatement of AL feeding. The effect of chronic CR on the sulfhydryl content of the brain cortex was only partially reversible. The introduction of CR for 6 weeks in the old mice resulted in a reduction of protein oxidative damage (as indicated by whole brain carbonyl content and cortex sulfhydryl), although this effect was not equivalent to that of CR from 4 months of age. The introduction of CR did not affect the sulfhydryl content of the heart. Overall, the current findings indicate that changes in the level of caloric intake may reversibly affect the concentration of oxidized proteins and sufhydryl content. In addition, chronic restriction of caloric intake also retards the age-associated accumulation of oxidative damage. The magnitude of the reversible and chronic effects appears to be dependent upon the tissue examined and the nature of the oxidative alteration.

Aging↗

PubMed1981

Prevention of age-related hypertriglyceridemia by caloric restriction and exercise training in the rat.

Plasma triglyceride concentrations were determined in three experimental groups of rats as they grew from 1 1/2-12 mo of age. One group was kept sedentary and allowed food ad lib (control), the second group was allowed to eat and exercise in a running wheel ad lib, and the third calorically-restricted in order to maintain weight equal to that of the exercising rats. The exercise-trained and calorically-restricted rats gained less weight than did the control rats, and the age-related rise in plasma triglyceride concentration in control rats was totally abolished in the other two groups. In addition, exercise training and caloric restriction inhibited the increase in plasma insulin concentrations noted to occur with age in the control rats. These data indicate that there are two effective ways to prevent the development of hypertriglyceridemia that occurs with age in otherwise normal rats.

Aging↗

PubMed2006

Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss.

Caloric restriction (CR) results in fat loss; however, it may also result in loss of muscle and thereby reduce strength and aerobic capacity (VO2 max). These effects may not occur with exercise-induced weight loss (EX) because of the anabolic effects of exercise on heart and skeletal muscle. We tested the hypothesis that CR reduces muscle size and strength and VO2 max, whereas EX preserves or improves these parameters. Healthy 50- to 60-yr-old men and women (body mass index of 23.5-29.9 kg/m2) were studied before and after 12 mo of weight loss by CR (n = 18) or EX (n = 16). Lean mass was assessed by dual-energy X-ray absorptiometry, thigh muscle volume by MRI, isometric and isokinetic knee flexor strength by dynamometry, and treadmill VO2 max by indirect calorimetry. Both interventions caused significant decreases in body weight (CR: -10.7 +/- 1.4%, EX: -9.5 +/- 1.5%) and lean mass (CR: -3.5 +/- 0.7%, EX: -2.2 +/- 0.8%), with no significant differences between groups. Significant decreases in thigh muscle volume (-6.9 +/- 0.8%) and composite knee flexion strength (-7.2 +/- 3%) occurred in the CR group only. Absolute VO2 max decreased significantly in the CR group (-6.8 +/- 2.3%), whereas the EX group had significant increases in both absolute (+15.5 +/- 2.4%) and relative (+28.3 +/- 3.0%) VO2 max. These data provide evidence that muscle mass and absolute physical work capacity decrease in response to 12 mo of CR but not in response to a similar weight loss induced by exercise. These findings suggest that, during EX, the body adapts to maintain or even enhance physical performance capacity.

Adaptation, Physiological↗

PubMed1996

Caloric restriction increases the expression of heat shock protein in the gut.

OBJECTIVE: The authors determined whether caloric restriction (CR) either acutely or chronically, alters heat shock protein 70 (hsp70) gene expression in the gut. SUMMARY BACKGROUND DATA: Caloric restriction prolongs the life span and delays age-related disease (e.g., cancer) in mammals; the mechanisms responsible for these effects are not known. Heat shock proteins are a group of stress-responsive genes of which the most prominent member is hsp70. METHODS: In the first experiment, adult (4-month-old) rats (n = 3/group) were killed after a 48-hour fast or 6 and 24 hours after refeeding. In addition, three rats (controls) were killed without fasting or refeeding. The stomach was removed and RNA was extracted for hsp70 gene expression. In the second experiment, aged (22- to 26-month-old) rats were fed ad libitum (AL) or a CR diet (60% caloric intake of AL diet). Rats were killed, the stomach and duodenum were removed, and RNA was extracted for determination of hsp70 gene expression. RESULTS: In the first experiment, hsp70 mRNA levels were increased approximately threefold in the stomach of rats fasted for 48 hours; levels decreased to control values by 6 and 24 hours after refeeding. In the second experiment, hsp70 mRNA levels were increased significantly in both the stomach and duodenum of aged CR rats compared with AL controls. CONCLUSIONS: The authors have demonstrated that hsp70 mRNA levels are increased in the proximal gut of young and old rats, either acutely (with fasting) or with CR. Increased expression of the cytoprotective hsp70 gene in the gut may provide a possible cellular mechanism for the beneficial effects noted with CR.

Aging↗