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Results for “Caloric Restriction”

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PubMed1989

Response of mammary tumors to caloric restriction for different time periods during the promotion phase.

Rats treated with 7,12-dimethylbenz[a]anthracene were subjected to 25% caloric restriction for varying times during the promotion/progression phase of mammary tumorigenesis. Caloric restriction was inhibitory to a statistically significant extent when it was maintained for the entire four-month study or only during the first or last two months. Restriction for the first month with subsequent ad libitum feeding led to rapid weight gain with concomitant appearance of tumors. These data indicate that caloric restriction can be instituted late in the tumorigenic process with an acute response of tumor growth to caloric intake or body weight.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1997

Effects of age and long-term caloric restriction on the aqueous collecting channel in the mouse eye.

PURPOSE: The mouse aqueous collecting channel, part of the mouse aqueous outflow pathway, was measured using a computer-assisted image analysis system. We used ad libitum-fed and calorie-restricted mice to investigate the effects of age and long-term caloric restriction on the lumen size of the channel. RESULTS: The ad libitum-fed mice showed a significant age-related reduction in the lumen area. In the ad libitum-fed group, the lumen area of the channel decreased by 30% at 30-35 months of age (p < 0.01), and the anteroposterior width declined by 21% (p < 0.001) as compared with mice 3-5 months of age. The calorie-restricted mice did not display any reduction with age in the lumen area or the anteroposterior width of the channel. When compared with the age-matched calorie-restricted mice, the lumen area of the channel of the ad libitum-fed mice measured less by 34%, and anteroposterior width less by 21% at 30-35 months of age (p < 0.01). CONCLUSIONS: These results indicate that an age-related morphological alteration in the mouse aqueous collecting channel occurred and that it is delayed by long-term caloric restriction. This suggests a possible role of life-long caloric restriction in reducing glaucomatous damages and perhaps delaying glaucoma development.

Aging↗

PubMed2001

Age-related telomere shortening occurs in lens epithelium from old rats and is slowed by caloric restriction.

We have investigated whether the average relative telomere length of lens epithelial cells (LECs) from brown Norway rats decreases with the age of the donor animal, and whether chronic caloric restriction (CR) of the rats delays the telomere shortening. Our previous studies have demonstrated that clonal proliferative potential of rodent LECs as well as the in vivo rate of DNA synthesis decreases with age and that this decrease is slowed by chronic lifelong caloric restriction (CR). In order to determine if telomeric shortening might be involved in this loss of proliferative potential, we examined relative telomeric lengths in young, old ad lib fed (AL), and old calorically restricted (CR) brown Norway rats. We used fluorescence in situ hybridization with a peptide nucleic acid probe (PNA) complementary to the telomeric repeat sequence to quantitate relative telomere lengths in LECs in lens sections (TELO-FISH). Control experiments demonstrated that the PNA probe binding was restricted almost entirely to the terminal portions of the rat chromosomes with less than 5% bound at interstitial sites in typical metaphase spreads. The relative telomere lengths of interphase human fibroblast standards, as determined by TELO-FISH, were in good agreement with terminal restriction fragment analyses of the same standards and with literature values for rat cells. The average telomere lengths of interphase nuclei in the old AL rat LECs were found to be 21% shorter than paired young AL controls (P < 0.01 by Wilcoxian signed rank test). The calorically restricted old rats had less telomere erosion (12%) than the old AL group (P < 0.05). Although it is not clear whether such moderate telomeric erosion can limit cell division in rodent LECs, the telomeric shortening correlated well with previous studies demonstrating reduced clonal, replicative potential, and reduced rates of in vivo DNA replication in LECs from old rodents and a delay in this attenuation in animals on chronic CR.

Aging↗

PubMed2003

Toxicokinetics of chloral hydrate in ad libitum-fed, dietary-controlled, and calorically restricted male B6C3F1 mice following short-term exposure.

Chloral hydrate is widely used as a sedative in pediatric medicine and is a by-product of water chlorination and a metabolic intermediate in the biotransformation of trichloroethylene. Chloral hydrate and its major metabolite, trichloroacetic acid, induce liver tumors in B6C3F1 mice, a strain that can exhibit high rates of background liver tumor incidence, which is associated with increased body weight. This report describes the influence of diet and body weight on the acute toxicity, hepatic enzyme response, and toxickinetics of chloral hydrate as part of a larger study investigating the carcinogenicity of chloral hydrate in ad libitum-fed and dietary controlled mice. Dietary control involves moderate food restriction to maintain the test animals at an idealized body weight. Mice were dosed with chloral hydrate at 0, 50, 100, 250, 500, and 1000 mg/kg daily, 5 days/week, by aqueous gavage for 2 weekly dosing cycles. Three diet groups were used: ad libitum, dietary control, and 40% caloric restriction. Both dietary control and caloric restriction slightly reduced acute toxicity of high doses of chloral hydrate and potentiated the induction of hepatic enzymes associated with peroxisome proliferation. Chloral hydrate toxicokinetics were investigated using blood samples obtained by sequential tail clipping and a microscale gas chromatography technique. It was rapidly cleared from serum within 3 h of dosing. Trichloroacetate was the major metabolite in serum in all three diet groups. Although the area under the curve values for serum trichloroacetate were slightly greater in the dietary controlled and calorically restricted groups than in the ad libitum-fed groups, this increase did not appear to completely account for the potentiation of hepatic enzyme induction by dietary restriction.

Animals↗

PubMed1997

Long-term caloric restriction delays age-related decline in proliferation capacity of murine lens epithelial cells in vitro and in vivo.

PURPOSE: The goal of this study was to examine the effects of age and long-term caloric restriction on the proliferation capacity of murine lens epithelial (LE) cells in vitro and in vivo. METHODS: B6D2F1 (C57BL/6 X DBA/2) F1 mice 4 to 45 months of age were obtained and fed either an ad libitum (AL) or a calorically restricted (CR) diet (60% of AL intake). Cellular proliferation capacity in vitro was measured using the colony size distribution assay for 10-day clonal growth of mouse LE cells. Proliferation rate in vivo was assayed using immunostaining for 5-bromo-2'-deoxyuridine (BrdU) in mouse LE cells after 2-week osmotic pump delivery of BrdU. RESULTS: Proliferative capacity of cells from old AL mice decreased significantly in comparison to cells from young AL and old CR mice, as determined by the fractions of cells capable of forming small (no or one cell division) and large (four or more cell divisions) colonies in vitro. There was also a decline in cell replicative rate as measured by BrdU labeling index (LI) in vivo with increasing age in AL and CR mice. However, this decline was marked in AL mice between 10 and 30 months of age and minimal in CR mice. Significant differences in BudU LI between AL and CR mice occurred when animals were 30 months of age or older. This finding indicates that an age-related decline in cellular proliferation rate in vivo was delayed by CR. CONCLUSIONS: A significantly reduced proliferative capacity of LE cells is associated with increased age of mice and is delayed by long-term caloric restriction as measured in vitro and in vivo. How caloric restriction mediates its effects on LE cell proliferation remains to be investigated further.

Aging↗

PubMed1999

Effects of lifelong moderate caloric restriction on levels of neuropeptide Y, proopiomelanocortin, and galanin mRNA.

We are interested in how neuropeptides that regulate both food intake and reproductive function change with age and how life-prolonging moderate caloric restriction may influence the expression of these neuropeptides. We measured neuropeptide Y (NPY) and proopiomelanocortin (POMC) mRNA in the arcuate nucleus (AN), and galanin (GAL) mRNA in the AN, paraventricular nucleus (PVN) and medial septum-diagonal band of Broca in young, middle-aged and old female rats on a controlled feeding regimen. Female Sprague-Dawley rats (7 weeks old) were placed on caloric restriction (CR; n = 70) which was 60% of ad libitum (AL) intake measured in control rats (n = 70). Rats were rapidly decapitated 2.5 weeks following ovariectomy, when they were 4, 12, or 18 months old. Brains were frozen and coronal sections (12 microns) were cut at -20 degrees C using a cryostat. Relative levels of NPY, POMC and GAL mRNA were measured using in situ hybridization histochemistry. cDNA clones complementary to rat NPY, mouse POMC and rat GAL were used to synthesize 35S-UTP-labeled cRNA probes. Slides were dipped in photographic emulsion. Silver grains were quantified using computer-assisted image analysis. Caloric restriction increased NPY mRNA/cell, decreased POMC mRNA/cell in the AN, and did not influence GAL mRNA/cell. Age and caloric restriction did not influence the number of cells with detectable NPY mRNA, POMC mRNA or GAL mRNA. Reproductive status at the time of decapitation influenced both the level and the number of cells expressing GAL mRNA in the PVN. In summary, CR differentially affects levels of NPY, POMC and GAL mRNA in the AN. In this animal model, there was no statistically significant effect of age nor any interaction between age and diet on expression of any of these genes between 4 and 18 months of age.

Aging↗

PubMed2000

Caloric restriction prevents age-related deficits in LTP and in NMDA receptor expression.

A major focus of aging research has been the search for treatments that will prevent or ameliorate the memory deficits associated with aging. One paradigm, lifelong caloric restriction, has been reported to reduce some of the effects of aging. In the current report, we examined the effects of this treatment on age-related deficits in LTP, a putative cellular building block for memory formation. We report here that lifelong caloric restriction completely prevents the age-related deficit in LTP. In addition, we report that there is a dramatic decrease in the expression of the NMDA receptor subunit NR1 in aged rats and this age-related defect is also prevented by caloric restriction. These data provide a molecular and cellular mechanism by which life long caloric restriction may ameliorate some of the cognitive deficits associated with the aging process.

Aging↗

PubMed2002

Effects of caloric restriction and aging on the auditory function of rhesus monkeys (Macaca mulatta): The University of Wisconsin Study.

The present study is part of a larger project that investigates the effect of caloric restriction on longevity in the rhesus monkey. The purpose of the present study was to document presbycusis and the effect of caloric restriction on presbycusis in monkeys. The control group had 35 monkeys allowed to eat freely and the caloric-restricted group (CR) had 33 monkeys with a 30% reduction in caloric intake. Monaural and binaural auditory brainstem response (ABR) and middle latency response (MLR) were obtained from 27 female and 41 male monkeys that were 11-23 years of age and had been in the study for 102, 42, or 36 months when tested. Significant findings were the following: (1) wave I amplitudes were larger for females and for younger monkeys, and amplitudes decreased in aging males but not in aging females; (2) wave IV amplitudes were larger for females than males, and amplitudes for CR females were larger than for female controls, whereas the amplitudes from control and CR males were not different; (3) wave Pa latencies were shorter for females, and shorter latencies were maintained for aging females but not for aging males; (4) interwave interval IV-Pa was shorter for females, and intervals lengthened for aging males but not aging females; (5) binaural wave IV amplitude decreased faster with age for control monkeys than for CR monkeys, and the L+R Pa amplitude decreased with age. Additional trends were identified for longitudinal monitoring as monkeys enter old age.

Aging↗

PubMed2004

Tissue-specific effect of refeeding after short- and long-term caloric restriction on malic enzyme gene expression in rat tissues.

Restricting food intake to a level below that consumed voluntarily (85%, 70% and 50% of the ad libitum energy intake for 3 or 30 days) and re-feeding ad libitum for 48 h results in an increase of malic enzyme (ME) gene expression in rat white adipose tissue. The increase of ME gene expression was much more pronounced in rats maintained on restricted diet for 30 days than for 3 days. The changes in ME gene expression resembled the changes in the content of SREBP-1 in white adipose tissue. A similar increase of serum insulin concentration was observed in all groups at different degrees of caloric restriction and refed ad libitum for 48 h. Caloric restriction and refeeding caused on increase of ME activity also in brown adipose tissue (BAT) and liver. However, in liver a significant increase of ME activity was found only in rats maintained on the restricted diet for 30 days. No significant changes after caloric restriction and refeeding were found in heart, skeletal muscle, kidney cortex, and brain. These data indicate that the increase of ME gene expression after caloric restriction/refeeding occurs only in lipogenic tissues. Thus, one can conclude that caloric restriction/refeeding increases the enzymatic capacity for fatty acid biosynthesis.

Adipose Tissue↗

PubMed2006

Humans are evolutionarily adapted to caloric restriction resulting from ecologically dictated dietary deprivation imposed during the Plio-Pleistocene period.

Humans are evolutionarily adapted to chronic undernutrition as a consequence of ecologically dictated dietary restriction. Increased aridity, cooler temperatures and increased climatic oscillation effected an alteration of the quantity and quality of vegetation upon which hominids depended for food during the Plio-Pleistocene period. Hominids responded physiologically to climate-induced caloric curtailment in the same way organisms respond to experimentally imposed caloric restriction: by reducing the rate and/or altering the manner in which they metabolized fuel. Such metabolic alterations are mediated principally by the hypothalamus and it is herein hypothesized that the human hypothalamus was subjected to substantial selective pressure, promoting an energetically conservative hypometabolic state. Moreover, the most salient phenotypic characteristics typifying the human species - long lifespan, low reproductive potential, lengthy development and high brain/bodyweight ratio - are effectuated in organisms undergoing caloric restriction. These phenotypic/physiological characteristics - herein termed the quadripartite complex - can be modulated by metabolic rate, which is, in turn, modulated by the hypothalamus. An appreciable alteration in climate occurred between 2.0 and 1.5 million years ago, a juncture at which one hominid lineage (Paranthropus) went extinct. Paranthropus was characterized by such external adaptations as robust cranio-facial morphology and pronounced enamel deposition, indicative of subsistence on tough, low-quality vegetal foods. Conversely, the Homo lineage responded to its marginal dietary repertoire through internal means, centering on metabolic suppression. It is herein hypothesized that this adaptive metabolic alteration, enacted in response to ecologically imposed caloric restriction, produced the defining morphologic attributes of Homo and enabled the evolutionary success of the human species. Among the implications of this line of thinking is that modern humans may be particularly sensitive to the deleterious effects of excess energy intake and, concomitantly, particularly amenable to the ameliorative effects of caloric restriction.

Adaptation, Physiological↗

PubMed2003

An in vitro model of caloric restriction.

The mechanisms underlying the ability of caloric restriction (CR) to extend life span and enhance stress responsiveness remain elusive. Progress in this area has been slow due to the complexities of using animals for CR studies and assessing life span as the measure of CR effectiveness. It is therefore of great interest to develop in vitro models of CR. Here we use sera obtained from either Fisher 344 rats or Rhesus monkeys that were fed ad libitum (AL) or CR diets to culture various cell types. We show that treatment of cultured cells with CR sera caused reduced cell proliferation, enhanced tolerance to oxidants and heat, and heightened expression of stress-response genes. These phenotypic features mirror the effects of CR in animals. Supplementation of CR serum with insulin and insulin-like growth factor (IGF)-1 partially restored the proliferative and stress-response phenotype that was seen in cells cultured with AL serum, indicating that reduced levels of insulin and IGF-1 likely contribute to the CR-related effects. This in vitro cell culture model recapitulates key in vivo proliferative and stress-response phenotypic features of CR, and further suggests that endocrine mechanisms contribute to the enhanced stress responsiveness observed in CR animals.

Animals↗

PubMed2003

Mitochondrial dysfunctions during aging: vitamin E deficiency or caloric restriction--two different ways of modulating stress.

Caloric restriction (CR), which has been demonstrated to offset the age-associated accrual of oxidative injury, involves a reduction in calory intake while maintaining adequate nutrition, preserves the activities of antioxidant enzymes in postmitotic tissues, maintains organ function, opposes the development of spontaneous diseases, and prolongs maximum life span in laboratory rodents. It has been proposed that reductions in Reactive Oxygen Species (ROS) production and cellular oxidative injury are central to the positive effects of CR. In the present investigation we studied the effect of CR and of a vitamin E deprived diet on mitochondrial structure and features in the liver of rats during aging, in order to ascertain the extent of modifications induced by these experimental conditions. CR rats displayed structural and functional mitochondrial properties (fatty acid pattern, respiratory chain activities, antioxidant levels, and hydroperoxide contents) similar to those of younger rats whilst vitamin E deficient rats appeared older than their own age. The mitochondria of the former, together with those of young rats, possessed the lowest Coenzyme Q9, hydroperoxide, and cytochrome contents as well as a suitable fatty acid membrane composition. Our study confirms that CR is a valuable tool in limiting aging-related free-radical damage also at mitochondrial liver level.

Adaptation, Physiological↗

PubMed1985

Adrenergic regulation of lipolysis in abdominal adipocytes of obese subjects during caloric restriction: reversal of catecholamine action caused by relief of endogenous inhibition.

The effects of adrenaline, noradrenaline, and of the alpha 2- and beta-selective agonists clonidine and isoproterenol were studied in fifteen obese subjects before and after 4 weeks of caloric restriction (300 cal day-1). Basal glycerol release averaged 1.4 mumol (10(6) cells)-1 (180 min)-1 before starvation and 2.8 mumol (10(6) cells)-1 (180 min)-1 during starvation (P less than or equal to 0.1). Before starvation adrenaline and noradrenaline caused a 2-3-fold increase of glycerol release. This lipolytic effect disappeared during starvation. An inhibitory effect of adrenaline was observed instead which was maximal at an adrenaline concentration of 1 mumol 1(-1) (P less than or equal to 0.05). The dose-response relationships of the alpha 2- and beta-selective agents clonidine and isoproterenol were not appreciably changed by caloric restriction. The increase of basal lipolytic rate and the reversal of adrenaline action seen during caloric restriction could be mimicked by removal of endogenous adenosine using adenosine deaminase (1.6 microgram ml-1). In addition, inclusion of N6-phenylisopropyladenosine (1 mumol 1(-1)) into the medium reverted the adrenaline-induced inhibition seen during caloric restriction. The results suggest that local modulators such as adenosine are of primary importance for the apparent change of responsiveness to adrenaline and noradrenaline seen during starvation of human fat cells in vitro.

Adenosine↗

PubMed1998

Short- and long-term changes in serum leptin dieting obese women: effects of caloric restriction and weight loss.

This study examined the effects of caloric restriction and weight loss on serum leptin concentrations in 49 obese women who participated in a 40-week weight loss program. During the first 12 weeks, half the subjects were provided a 1000 kcal/day low-calorie diet (LCD), compromised of portion-controlled foods, whereas the other half were prescribed a 1200 kcal/day balanced deficit diet (BDD) consisting of self-selected table foods. Thereafter, subjects in both conditions were instructed to consume approximately 1200-1800 kcal/day of self-selected foods, depending on their desired weight change. During the first 6 weeks, weight and serum leptin fell significantly more (P < 0.05) in women in the LCD condition than in the BDD condition. In the former group, the 55% reduction in baseline leptin was 10 times greater than the relative reduction in body weight. Stepwise multiple regression analysis revealed that degree of caloric restriction, but not weight loss, contribution significantly to the variance in the change in leptin at week 6. By contrast, long-term changes in leptin, when subjects had increased their calorie intake, were more strongly related to changes in weight and fat. At week 40, for example, weight loss account for 47% of the variance in the change in leptin. Serum leptin and body fat remained highly correlated after weight loss (r = 0.79, P < 0.001), as before (r = 0.66, P < 0.001). After treatment, however, we observed a greater-than-expected reduction in serum leptin concentrations, as expressed per kilogram of body fat. The significance of this finding remains to be determined.

Adipose Tissue↗

PubMed2004

Effects of age and caloric restriction on brain neuronal cell death/survival.

Aging may pose a challenge to the central nervous system, increasing its susceptibility to apoptotic events. Recent findings indicate that caloric restriction (CR) may have a profound effect on brain function and vulnerability to injury and diseases, by enhancing neuroprotection, stimulating the production of new neurons, and increasing synaptic plasticity. Apoptosis and apoptotic regulatory proteins in the brain frontal cortex of 6-month-old ad libitum fed (6AD), 26-month-old ad libitum fed (26AD), and 26-month-old caloric-restricted (26CR) male Fischer 344 rats (40% restriction compared to ad libitum fed) were investigated. Levels of Poly-ADP ribose polymerase (PARP-DNA repair enzyme; its cleaved 89 kDA fragment is a marker of apoptosis), cytoplasmic histone-associated DNA fragments, and X chromosome-linked inhibitor of apoptosis (XIAP--an endogenous apoptosis inhibitor) were determined. A significant age-associated increase in PARP was found, which was ameliorated in the frontal cortices of the CR rats. No significant differences in cytoplasmic histone-associated DNA fragments with age or with CR were observed. XIAP levels significantly increased with age in the brains of the ad libitum animals, while CR animals exhibited the highest levels of this inhibitor compared to all groups. Our findings suggest that caloric restriction may provide neuroprotection to the aging brain by preserving DNA repair enzymes in their intact form, and/or upregulating specific antiapoptotic proteins involved in neuronal cell death.

Aging↗

PubMed1995

Moderate caloric restriction alters the subcellular distribution of somatostatin mRNA and increases growth hormone pulse amplitude in aged animals.

Although growth hormone secretion decreases with age in both animals and man, its potential role in the regulation of biological aging is unknown. In a series of experiments, age-related changes in growth hormone secretory dynamics were compared in ad libitum fed and moderately calorically restricted male Brown-Norway rats. These animals exhibit an increase in both mean and maximal lifespan in response to caloric restriction. In addition, the subcellular distribution of somatostatin mRNA was compared since previous data indicated that somatostatin secretion increases with age and has an important role in the age-related decline in growth hormone pulse amplitude. In ad libitum fed animals, growth hormone secretory dynamics decreased with age and were associated with a decline in total somatostatin mRNA levels. However, analysis of somatostatin mRNA precipitating with polyribosomes revealed a significant increase with age (p < 0.05). When data were expressed as polysomal/total mRNA, levels in 25-month-old animals increased 94 and 104% compared to 6- or 16-month-old animals, respectively (p < 0.01). Growth hormone secretory dynamics decreased in young animals maintained on a moderate caloric restricted diet, but by 26 months growth hormone pulse amplitude increased and was indistinguishable from young ad libitum fed animals. In addition, the moderate caloric-restricted animals failed to exhibit the decline in total somatostatin mRNA or the increase in polyribosome-associated somatostatin mRNA characteristic of the ad libitum fed 25-month-old animals. Our results suggest that altered regulation of somatostatin mRNA at the translational level may be a contributing factor in the decrease in growth hormone secretion observed in aging animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed2005

Effect of insulin and growth hormone on rat heart and liver oxidative stress in control and caloric restricted animals.

In order to know if insulin-like signalling is involved in the control of oxidative stress in mammalian tissues in relation to aging, ad libitum-fed and caloric restricted Wistar rats were treated during 2 weeks with GH and insulin. The most consistent effect of the hormonal treatments was an increase in plasma IGF-1 levels. Caloric restriction during 6 weeks decreased ROS generation and oxidative DNA damage in heart mitochondria and this was reversed by insulin treatment. The decrease in oxidative damage to liver nuclear DNA induced by caloric restriction was also reversed by GH and insulin. In the liver, however, insulin and GH decreased mitochondrial ROS generation while they increased oxidative damage to mitochondrial DNA. GH and insulin decreased three different markers of oxidative modification of liver proteins, while they increased lipoxidation-dependent markers. This last result is related to the increase in phospholipid unsaturation induced in the liver by both hormones. The results suggest that the idea that insulin-like signalling controls oxidative stress in mammals cannot be generalized since both prooxidant and protective effects of GH and insulin are observed depending on the particular parameter and tissue selected.

Age Factors↗

PubMed1996

Enhanced cell proliferation and biosynthesis mediate improved wound repair in refed, caloric-restricted mice.

Aged mice that have undergone long-term caloric-restriction (CR) have improved health and enhanced longevity in comparison to aged mice that are ad libitum-fed (AL). However, caloric-restriction does not benefit the impaired wound healing of aged mice. To test the hypothesis that CR mice have the capacity for enhanced wound repair, but require a short-term period of additional nutrient intake to show this advantage, we assessed wound healing in CR mice that had been refed (RF) an ad libitum diet for 4 weeks prior to wounding. Two strains of AL young (Y AL) (4-6 months), AL middle-aged (M AL) (15-17 months), and three different, matched cohorts of old mice (O) (30-33 months): O AL, O CR, and O RF were studied. Two full-thickness 4 mm diameter punch biopsy skin wounds were created on the dorsum of each mouse. Animals were sacrificed and wounds were harvested at 1,2,3,5, and 7 days post-wounding. Repair of wounds was slower in O AL and O CR mice compared to Y AL and M AL animals. In contrast, the O RF mice healed similarly to that of the Y AL and M AL mice, as assessed by measures of wound area and histologic criteria. O RF mice demonstrated enhanced synthesis of type I collagen mRNA in comparison to O AL and O CR mice. A greater number of endothelial cells and fibroblasts at the wound edge of the O RF mice exhibited replication in vivo as measured by uptake of BrdU. O RF mice had higher levels of insulin-like binding protein 3 (IGFBP-3). Furthermore, fibroblasts derived from the explant of the punch biopsy of O CR mouse skin revealed enhanced proliferation and contraction in vitro, in comparison to fibroblasts from the O AL mice. In conclusion, O RF mice demonstrate an enhanced capacity to undergo wound repair in comparison to O AL mice. This effect appears to be mediated, in part, by enhanced cell proliferation, contraction, and collagen biosynthesis. In addition, short-term refeeding induced an increase in the serum level of IGFBP-3, the major binding protein for IGF-1. These data confirm that cells from O CR animals have a preserved proliferative, biosynthetic, and contractile capacity, but that an adequate source of nutrients is necessary to demonstrate this advantage in wound healing.

Aging↗