SEARCH · PubMed Health

Results for “Caloric Restriction”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources

PubMed2004

Effect of ageing and caloric restriction on specific markers of protein oxidative damage and membrane peroxidizability in rat liver mitochondria.

To gain insight into the anti-ageing mechanisms of caloric restriction (CR), liver mitochondria were isolated from male Brown-Norway rats of different ages (fully fed control and CR) and various specific markers of non-enzymatic protein modification (by oxidative, glyco- and lipoxidative-reactions) were measured by GC/MS and Western blotting. A membrane peroxidizability index (PI) was calculated from the fatty acid profiles. Between 6 and 18 months of age, there were significant decreases in the concentration of all markers of damage in mitochondria from both the fully fed and CR groups. In contrast, between the ages of 18 and 28 months, there were significant increases in the concentrations of all markers of damage. In mitochondria from both fully fed and CR groups, there were significant increases in N-epsilon (Nepsilon)-(carboxymethyl)lysine (CML) and N-epsilon-(malondialdehyde)lysine (MDAL) between 6 and 28 months of age. In general, damage tended to be lower in mitochondria from CR animals, but the effects were not significant, except for the concentration of N-epsilon-(carboxymethyl)lysine at 28 months of age. PI increased steadily and significantly with age in fully fed animals, whilst CR induced a significant decrease in this index at 28 months of age. It is concluded that for male rats of the Brown-Norway strain, and mitochondria from liver (i) old (but not mature) age is associated with an increased membrane PI and protein oxidative damage and (ii) CR does not lead to a general reversion in age-related protein damage, but it does prevent the age-induced increase in PI very late in life.

Aging↗

PubMed2001

Caloric restriction alters the feeding response of key metabolic enzyme genes.

Differential 'fuel usage' has been proposed as a mechanism for life-span extension by caloric restriction (CR). Here, we report the effects of CR, initiated after weaning, on metabolic enzyme gene expression 0, 1.5, 5, and 12 h after feeding of 24-month-old mice. Plasma glucose and insulin were reduced by approximately 20 and 80%. Therefore, apparent insulin sensitivity, as judged by the glucose to insulin ratio, increased 3.3-fold in CR mice. Phosphoenolpyruvate carboxykinase mRNA and activity were transiently reduced 1.5 h after feeding, but were 20-100% higher in CR mice at other times. Glucose-6-phosphatase mRNA was induced in CR mice and repressed in control mice before, and for 5 h following feeding. Feeding transiently induced glucokinase mRNA fourfold in control mice, but only slightly in CR mice. Pyruvate kinase and pyruvate dehydrogenase activities were reduced approximately 50% in CR mice at most times. Feeding induced glutaminase mRNA, and carbamyl phosphate synthetase I and glutamine synthase activity (and mRNA). They were each approximately twofold or higher in CR mice. These results indicate that in mice, CR maintains higher rates of gluconeogenesis and protein catabolism, even in the hours after feeding. The data are consistent with the idea that CR continuously promotes the turnover and replacement of extrahepatic proteins.

Aging↗

PubMed2000

Use of primary cultures of rat hepatocytes for the study of ageing and caloric restriction.

Primary cultures of hepatocytes are widely used to investigate liver function, but this technology has not been exploited fully in the study of ageing and caloric restriction (CR). Hepatocytes were isolated from adult and aged, fully fed, and calorie restricted male Sprague-Dawley rats and their viability and biochemical status assessed over 48h in primary culture. The in vivo differences in cellular protein and DNA content due to age and CR were maintained over the 48h experimental period. The results of this study confirm earlier reports that protein synthesis and degradation rates decline with age in liver tissue, and this decline is retarded by CR. Rates of protein synthesis and degradation in the first year of life were depressed in response to CR feeding and were only significantly higher than recorded for control animals during the second year of life. Cells from rats of both ages and diets maintained linear rates of extracellular protein synthesis, intracellular protein synthesis, protein degradation and albumin secretion between 24 and 48h in culture. These findings indicate that hepatocytes from CR rats did not respond adversely to the relatively rich culture medium and cells from CR animals did not immediately revert to the fully fed phenotype.

Aging↗

PubMed1986

Phenylpropanolamine OROS (Acutrim) vs. placebo in combination with caloric restriction and physician-managed behavior modification.

We added phenylpropanolamine OROS (Acutrim; Ciba-Geigy Corp.) or placebo to a physician-managed behavior modification, mild caloric restriction, and exercise weight control program. One hundred six healthy, overweight (115% to 130% ideal body weight) women participated in this 14-week double-blind clinical trial. On average, the participants who took Acutrim lost significantly more weight (X +/- SE; 6.1 +/- 0.6 kg; 8.0% +/- 0.8%) than did those taking placebo (4.3 +/- 0.7 kg; 5.5% +/- 0.8%; P less than 0.05). Those taking Actrim continued to lose weight over the Christmas holiday, while the placebo group gained weight. Fifteen participants taking placebo withdrew, three because of adverse drug reactions (ADRs). Thirteen of 53 participants in the Acutrim group left the study, two because of ADRs. Dry mouth was the most frequent complaint from participants taking Acutrim. No serious cardiovascular effects occurred. Both complaints and the number of participants reporting ADRs decreased with continued dosing. We conclude that Acutrim is a safe, modestly effective adjunct to a physician-managed, integrated weight control program.

Adolescent↗

PubMed2001

Genetic variability in responses to caloric restriction in animals and in regulation of metabolism and obesity in humans.

Panel 5 focused on genetic factors that might mediate or moderate the effects of caloric restriction (CR) on longevity. Panel members stated that currently there is limited information directly addressing these issues. Therefore, they focused attention on what studies could be done. In addition, the panel believed that certain conceptual issues merited clarification and focused attention on this issue. Human studies and studies of nonhuman model organisms were discussed. The panel found at least three reasons why it would be valuable to find genes that influence the (putative) longevity-promoting effect of CR in humans. Such knowledge would offer: (a) the ability to predict individual responses to CR; (b) increased understanding of physiological mechanisms; and (c) the potential to develop mechanism-based interventions to promote longevity or healthy aging. In addition, the panel emphasized several macro-level recommendations regarding research strategies to avoid, research strategies to emphasize, and resources needing development.

Animals↗

PubMed2002

Oxidative phosphorylation enzyme complexes in caloric restriction.

Free radicals, generated especially by electron leakage from mitochondrial electron transport chain (ETC), are accepted as one of the possible causes of aging. Long-term caloric restriction (CR) is known to increase the species specific average and maximum life spans. Thus it provides a means for investigating mechanisms of aging. There is evidence suggesting a decrease in the free radical production with CR. In this study, Blue-Native PAGE (BN-PAGE) technique was used to investigate the effect of CR on the oxidative phosphorylation enzyme complexes. Of the total 30 female Swiss Albino balb/c mice, 15 were used as control and the other 15 as CR group. Alternate day feeding regimen was used in the CR group for 66 weeks beginning at the end of 3rd month. In the control group, 5 (33.3%) mice died, 3 (20%) of them of breast cancer, 2 (13.3%) of unknown causes and no death cases were observed in the CR group during the study. BN-PAGE was performed on the extracts from brain mitochondrial fractions. Complexes II and V were excluded from the study due to some analytical limitations. No difference was found in the levels of complexes I and III between the groups. In the CR group, complex IV level was found increased and the ratio of complex III-IV decreased compared with the control group. Since there is a slight increase (108%) in the level of complex IV in the CR group, our results could suggest possible partial compensation of electron leakage in the upstream complexes in ETC, and the decrease of free radical production with CR.

Adenosine Triphosphatases↗

PubMed2001

Leptin signaling and aging: insight from caloric restriction.

Organisms have evolved neuroendocrine and metabolic response systems to enhance survival during periods of food shortage, which occur frequently in nature. The anti-aging effect of caloric restriction (CR) might derive from these adaptive responses to maximize organism survival. The present article discusses the potential role for leptin, a hormone secreted from adipocytes, as a key signal that induces the adaptive responses relevant to CR. Evidence indicates that a CR-induced reduction of the plasma leptin concentration suppresses the gonadal, somatotropic, and thyroidal axes, and activates the adrenal axis. Metabolic adaptation, a shift in fuel utilization mainly conducted in the liver, seems to require leptin signaling. Although alternative signaling pathways might also mediate the anti-aging effects of CR, leptin signaling could be a substantial pathway involved in these effects. Molecular dissection of the mechanisms underlying the effects of CR will contribute to a better understanding of the aging process, leading to the extension of a healthy lifespan in humans.

Adaptation, Physiological↗

PubMed2002

Effects of caloric restriction on mitochondrial function and gene transcripts in rat muscle.

Rodent skeletal muscle mitochondrial DNA has been shown to be a potential site of oxidative damage during aging. Caloric restriction (CR) is reported to reduce oxidative stress and prolong life expectancy in rodents. Gene expression profiling and measurement of mitochondrial ATP production capacity were performed in skeletal muscle of male rats after feeding them either a control diet or calorie-restricted diet (60% of control diet) for 36 wk to determine the potential mechanism of the beneficial effects of CR. CR enhanced the transcripts of genes involved in reactive oxygen free radical scavenging function, tissue development, and energy metabolism while decreasing expression of those genes involved in signal transduction, stress response, and structural and contractile proteins. Real-time PCR measurements confirmed the changes in transcript levels of cytochrome-c oxidase III, superoxide dismutase (SOD)1, and SOD2 that were noted by the microarray approach. Mitochondrial ATP production and citrate synthase were unaltered by the dietary changes. We conclude that CR alters transcript levels of several genes in skeletal muscle and that mitochondrial function in skeletal muscle remains unaltered by the dietary intervention. Alterations in transcripts of many genes involved in reactive oxygen scavenging function may contribute to the increase in longevity reported with CR.

Adenosine Triphosphate↗

PubMed1994

Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients.

OBJECTIVE: To examine the effects of caloric restriction, independent of differences in weight loss, on improvements in glycemic control, fasting insulin, and insulin sensitivity. RESEARCH DESIGN AND METHODS: We randomized 93 obese type II diabetic patients to two different degrees of calorie restriction (1,674 or 4,185 kJ/day; 400 or 1,000 kcal/day) and compared the changes in fasting glucose, fasting insulin, and insulin sensitivity that resulted from a comparable reduction in body weight (11% of initial body weight). Insulin sensitivity was assessed using the minimal model analysis of frequently sampled intravenous glucose tolerance tests. RESULTS: Despite equal weight losses, subjects in the 1,674 kJ/day (400 kcal) condition had lower fasting glucose levels (7.61 vs. 10.13 mM, P = 0.03) and greater insulin sensitivity (1.79 vs. 1.13, P = 0.04) after weight loss than did subjects in the 4,185 kJ/day (1,000 calorie) condition. Subjects were restudied 15 weeks later when both groups were consuming a 4,185 kJ/day (1,000 kcal/day) diet. Subjects who increased from 1,674 to 4,185 kJ (400 to 1,000 calories) had worse fasting glycemic control in spite of continued weight loss, whereas subjects who remained on 4,185 kJ (1,000 calories) throughout had further improvements in both blood glucose and insulin sensitivity with increased weight loss. CONCLUSIONS: Both degree of calorie restriction and magnitude of weight loss have independent effects on improvements in glycemic control and insulin sensitivity.

Adult↗

PubMed2002

A new animal model of binge eating: key synergistic role of past caloric restriction and stress.

Dieting and stress are important in the etiology and maintenance of eating disorders, and dieting strongly predicts stress-induced overeating in humans. We hypothesized that caloric restriction and stress interact in a unique manner to promote binge eating. To test this hypothesis, a group of young female rats were cycled through a restriction period (4 days of 66% of control food intake) followed by 6 days of free feeding prior to being stressed by acute foot shock. After three of these cycles, the food intake of rats exposed only to restriction (R), or only to stress (S), did not differ from controls. However, R+S rats that were restricted and refed, despite normal body weight and food intake after free feeding, engaged in a powerful bout of hyperphagia when stressed (Experiment 1). The R + S effect was replicated in an older group of rats (Experiment 2). The hyperphagia was characteristically binge-like, it constituted a 40% selective increase in highly palatable (HP) food (P < .001) over a discrete period of time (within 24 h post-stress), and reflected feeding for reward (higher HP:chow ratio) over metabolic need as occurred after restriction (higher chow:HP ratio). Subsequent experiments revealed that binge eating did not occur if only chow was available (Experiment 3) or if restriction-refeeding (R-R) did not proximally precede stress (Experiment 4). Experiment 5 revealed that a history of R-R cycles followed by only one stress episode was sufficient to increase intake to 53% above controls as early as 2 h after stress (P < .001). This animal model of binge eating should facilitate investigations into the neurochemical changes induced by dieting and environmental stress to produce disordered eating and provide a preclinical tool to test preventive strategies and treatments more relevant to bulimia nervosa, multiple cases of binge eating disorder (BED) and binge-purge type anorexia nervosa.

Animals↗

PubMed1995

Caloric restriction: conservation of in vivo cellular replicative capacity accompanies life-span extension in mice.

In male mice of a long-lived hybrid strain (B6D2F1), long-term 40% caloric restriction (CR) extended both mean and maximum life spans by 36 and 20%, respectively, over that of ad libitum fed (AL) controls. Measurements of entry into S-phase were made in vivo of six different cell types in five different organs using 2-week exposures to BrdU. The labeling index (L.I.) in all organs studied was lower in young CR mice than in young AL fed mice. In most cases, the L.I. in AL mice fell to the levels of that in the CR mice by 13 months of age, and the two groups then remained so through old age. However, when the L.I. was measured in old CR mice which had been placed on the AL diet for a period of 4 weeks (this was termed refeeding (RF), it was found to be above that of similar age AL or CR mice and almost at the level of young AL mice. This was still true, but to a lesser degree, in a repeat study using an 8-week period of RF. In a separate but parallel in vitro study (companion paper, this volume), the superiority of CR over AL for retention of cellular replication capacity was confirmed by clone size distribution measurements made in several cell types in mice of several age groups. These results indicate that: (1) the rate of cell replication in AL diet mice diminishes greatly by early middle age in all organ sites studied and then plateaus or declines much more slowly; (2) CR broadly preserves in vivo cellular replicative capacity but often requires the energy levels provided by a switch to AL feeding to demonstrate this late in life; (3) accordingly, the replicative deficit in AL fed mice appears to be cumulative and is significant only in old age. The mechanism(s) involved is yet to be discovered but may be related to, or even the same as, that which extends life spans in CR animals. Correspondingly, and with corroborative data from our in vitro companion study, (W. R. Pendergrass et al., 1995. Exp. Cell. Res. 217, 309-316), we suggest that cell populations sustain an accrual of biochemical damage or physiological alterations which increasingly limit their replicative capacity as the animal ages, and that CR reduces the accrual of this damage.

Aging↗

PubMed1975

Diurnal variation in endogenous production of carbon monoxide. Effect of caloric restriction.

The endogenous production of carbon monoxide (VCO) and total serum bilirubin (SB) have been followed in five healthy male volunteers during one baseline day and one day with no caloric intake. VCO in the morning studies was 11.2+/-1.7 (mean +/-1 S.E.M.) on the baseline day and 10.1+/-2.3 mumol/mmol total body heme (TBH) and day on the fasting day, respectively. In studies before noon, VCO increased significantly on both days, to values of 17.8+/-1.6 and 19.6+/-2.2 mumol/mmol TBH and day, respectively. In the first study in the afternoon, VCO differed significantly between the two days, amounting to 12.1+/-3.0 and 23.7+/-3.5 on the baseline and the fasting day, respectively. The difference was still significant in the evening, when VCO was 11.6+/-3.1 and 22.1+/-4.9 mumol/mmol TBH and day. SB followed the same pattern, with mean values of 4.0+/-0.3, 4.9+/-0.3, 4.2+/-0.9 and 3.0+/-0.3 mug/ml during the baseline day and 4.5+/-0.6, 5.4+/-1.2, 7.0+/-0.5 and 8.5+/-1.0 mug/ml, respectively, during fasting day. Only insignificant amounts of conjugated bilirubin were found. The studies confirm earlier reports on the effect of caloric restriction on VCO. Since this effect is simultaneous with an increase in SB, it is concluded that the changes are secondary to an increase in total heme catabolism. They might be due to an increase in intracellular hepatic heme turnover but it cannot be excluded that starvation affects erythropoiesis and/or red cell catabolism, thereby causing an increase in VCO and SB.

Adult↗

PubMed1989

Caloric restriction and 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth in rats: alterations in circulating insulin, insulin-like growth factors I and II, and epidermal growth factor.

Caloric restriction (CR) inhibits many neoplastic diseases in rodents, yet the biochemical mechanism(s) for these effects are poorly understood. We have examined the effects of ad libitum (AL) feeding with 25 or 40% CR on the promotion of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in virgin female Sprague-Dawley rats. Further, we have also studied the influence of chronic CR on temporal alterations in circulating insulin, insulin-like growth factor I/somatomedin C, insulin-like growth factor II/multiplication-stimulating activity, and epidermal growth factor levels at 0, 1, 3, 5, 11, and 20 weeks in carcinogen- and vehicle-treated animals. Tumor incidence and multiplicity were markedly inhibited (P less than 0.05) with increasing CR. Fasting serum insulin-like growth factor I/somatomedin C levels exhibited a significant acute decline with CR at 1 and 3 weeks, but were comparable to AL-fed controls throughout the remainder of the 5-month study, despite continued differences in weight gain between AL and CR rats. Levels of insulin-like growth factor II/multiplication-stimulating activity exhibited no discernible pattern in relation to CR. Serum insulin levels showed age-dependent increases, but were affected by increasing CR at all time points. Insulin levels were significantly (P less than 0.05) reduced in 40% CR rats from 3 weeks onward compared to controls, while 25% CR resulted in nonsignificant (P less than 0.07) reductions throughout the study. No significant differences in growth factor levels were observed between 7,12-dimethylbenz(a)anthracene- and vehicle-treated rats. Circulating epidermal growth factor was not detectable in any treatment group regardless of the nature or duration of the dietary regimen, time of blood collection, or subsequent tumor-bearing status. These data suggest that decreased serum insulin-like growth factor I/somatomedin C and insulin levels with CR and their complex interactions in vivo may play a role in the inhibition of mammary tumor promotion by CR.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1995

Age-associated changes in mitogen-induced lymphoproliferation and lymphokine production in the long-lived brown-Norway rat: effect of caloric restriction.

We have previously demonstrated that age-related declines in Concanavalin A (ConA), induced proliferation and lymphokine production, occur in ad-libitum fed Brown Norway (AL BN) rats. Since caloric restriction (CR) extends lifespan, we expected that the age related changes in immune parameters would be delayed by CR. CR does act to delay age-related changes in proliferation in response to ConA. In addition, CR postpones the plateau in ConA induced interferon (IFN) production seen after 23 months of age in AL rats. However, CR does not postpone the age-related decline in ConA induced interleukin-2 (IL-2) production. Therefore, ConA induced IFN production maybe a good candidate as an early marker of physiologic aging, while ConA induced proliferative response is a possible candidate for a marker of late stages of aging.

Aging↗

PubMed1995

Exercise training and severe caloric restriction: effect on lean body mass in the obese.

The purpose of this study was to investigate the effects of exercise intensity on the body composition of obese subjects during severe caloric restriction. Forty obese subjects (33 women, 7 men; 41 +/- 7.7 years; 106 +/- 26kg; body fat > 25% men, > 30% women) on a commercially prepared OPTIFAST 420kcal/day supplemented fast were randomized into groups that exercised at target heart rates corresponding to 40% and 60% of the heart rate reserve (HRR) at the start of the program. Training volume was similar for both groups at approximately 300kcal per session three times per week for 12 weeks. Body weight, body fat, and lean weight were similar for both exercise intensity groups at week one. Overall, body weight decreased by 15.3 +/- 6.7 kg (p < or = .05), and body fat decreased by 14.9 +/- 5.0 kg (p < or = .05) for the 40 subjects, whereas lean weight remained unchanged. No significant differences in body weight, body fat, or lean weight were observed between the two groups. The results of the current study indicated that while on a supplemented 420-kcal/day fast, exercise at 40% and 60% of the HRR affected body composition similarly when total training volume was held constant at 900kcal/week. Lean weight remained unchanged and accompanied a 14.9 +/- 5.0-kg decrease in body fat, which may have resulted when the volume of exercise (ie, 900kcals/wk) was factored into the exercise prescriptions. These results suggest that exercising at 60% of the HRR offers no advantages for body composition changes over those obtained from exercising at 40% of HRR when the total volume of exercise training is controlled.

Adult↗

PubMed1994

One-year behavioral treatment of obesity: comparison of moderate and severe caloric restriction and the effects of weight maintenance therapy.

This study compared the weight losses of 49 obese women randomly assigned to a 52-week behavioral program combined with either moderate or severe caloric restriction. Subjects in the balanced deficit diet (BDD) condition were prescribed a 1,200-kcal/day diet throughout treatment, and those in the very-low-calorie diet (VLCD) condition were given a 420-kcal/day liquid diet for 16 weeks and a 1,200-kcal/day diet thereafter. The VLCD subjects lost significantly more weight than the BDD subjects at all periods through Week 26, at which time mean losses were 21.45 and 11.86 kg, respectively. VLCD subjects, however, regained weight during the next 26 weeks of weekly therapy and during a 26-week weight maintenance program that provided biweekly meetings. Mean weight losses at the end of the maintenance program were 10.94 and 12.18 kg, respectively. Reports of binge eating declined in both groups, and no relationship was observed between binge eating and weight loss or attrition.

Adult↗

PubMed1998

The effect of short periods of caloric restriction on weight loss and glycemic control in type 2 diabetes.

OBJECTIVE: To determine whether an intermittent very-low-calorie diet (VLCD) improves weight loss and glycemic control more than moderate caloric restriction alone. RESEARCH DESIGN AND METHODS: Individuals with type 2 diabetes (n = 54) who were > or = 20% over ideal body weight participated in a 20-week behavioral weight control program. Subjects were randomized to either a standard behavioral therapy (SBT) group or to one of two VLCD groups. SBT subjects received a 1,500-1,800 kcal/day diet throughout. Both VLCD groups followed a VLCD for 5 consecutive days during week 2, followed by either intermittent VLCD therapy for 1 day/week for 15 weeks (1-day) or for 5 consecutive days every 5 weeks (5-day), with a 1,500-1,800 kcal/day diet at other times. RESULTS: Both VLCD groups lost more weight than the SBT group over the 20 weeks (P = 0.04). Although the groups did not differ in fasting plasma glucose (FPG) changes at 20 weeks, more subjects in the 5-day group attained a normal HbA1c when compared with the SBT group (P = 0.04). This benefit was independent of the effects of weight loss. The best predictor of overall change in FPG and HbA1c was the FPG response during the first 3 weeks of the program. CONCLUSIONS: Periodic VLCDs improved weight loss in diabetic subjects. A regimen with intermittent 5-day VLCD therapy seemed particularly promising, because more subjects in this group attained a normal HbA1c. Moreover, the glucose response to a 3-week period of diet therapy predicted glycemic response at 20 weeks, and it was a better predictor of the 20-week response than initial or overall weight loss.

Adult↗

PubMed2000

Effects of aging and caloric restriction on IGF-I, IGF-I receptor, IGFBP-3 and IGFBP-4 gene expression in the rat stomach and colon.

The purpose of this study was to determine the effects of aging and caloric restriction (CR) on insulin-like growth factor-I (IGF-I), IGF-I receptor (IGF-IR), IGF-binding protein-3 (IGFBP-3) and IGFBP-4 expression in the stomach and colon of male Fischer 344 rats. Stomach and colonic RNA were prepared from ad libitum (AL) fed or long-term CR rats. Stomach IGF-I, IGFBP-3 and IGFBP-4 mRNA levels increased significantly (P</=0.05), while colonic IGF-I mRNA levels were unchanged in aged AL rats. In aged CR rats, stomach IGFBP-3 mRNA levels decreased. Stomach and colonic IGF-IR mRNA levels declined with aging in AL and CR rats (P</=0.05). Colonic IGFBP-3 mRNA levels decreased significantly with aging in AL rats. There were no changes in colonic IGFBP-4 mRNA levels in aged AL or CR rats. Increased expression of stomach IGF-I, IGFBP-3 and IGFBP-4 in aged AL rats suggests that the stomach attempts to preserve IGF activity by increasing local expression of IGF-I and IGFBPs. Because the aging colon has a propensity to develop cancer, it may adapt to increased colonic IGF-I expression by reducing IGF-IR and IGFBP-3 expression. Additionally, CR lowers colonic IGF-I expression in aged rats (24 months) which may also be a protective adaptive mechanism.

Aging↗