Skeletal effects of long-term caloric restriction in rhesus monkeys

Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, 53715, USA, .
Age (Impact Factor: 3.45). 12/2011; 34(5):1133-43. DOI: 10.1007/s11357-011-9354-x
Source: PubMed


Age-related bone loss is well established in humans and is known to occur in nonhuman primates. There is little information, however, on the effect of dietary interventions, such as caloric restriction (CR), on age-related bone loss. This study examined the effects of long-term, moderate CR on skeletal parameters in rhesus monkeys. Thirty adult male rhesus monkeys were subjected to either a restricted (R, n = 15) or control (C, n = 15) diet for 20 years and examined throughout for body composition and biochemical markers of bone turnover. Total body, spine, and radius bone mass and density were assessed by dual-energy X-ray absorptiometry. Assessment of biochemical markers of bone turnover included circulating serum levels of osteocalcin, carboxyterminal telopeptide of type I collagen, cross-linked aminoterminal telopeptide of type I collagen, parathyroid hormone, and 25(OH)vitamin D. Overall, we found that bone mass and density declined over time with generally higher levels in C compared to R animals. Circulating serum markers of bone turnover were not different between C and R with nonsignficant diet-by-time interactions. We believe the lower bone mass in R animals reflects the smaller body size and not pathological osteopenia.

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    ABSTRACT: Calorie Restriction (CR) without malnutrition slows aging and increases average and maximal lifespan in simple model organisms and rodents. In rhesus monkeys long-term CR reduces the incidence of type 2 diabetes, cardiovascular disease and cancer, and protects against age-associated sarcopenia and neurodegeneration. However, so far CR significantly increased average lifespan only in the Wisconsin, but not in the NIA monkey study. Differences in diet composition and study design between the 2 on-going trials may explain the discrepancies in survival and disease. Nevertheless, many of the metabolic and hormonal adaptations that are typical of the long-lived CR rodents did not occur in either the NIA or WNPRC CR monkeys. Whether or not CR will extend lifespan in humans is not yet known, but accumulating data indicate that moderate CR with adequate nutrition has a powerful protective effect against obesity, type 2 diabetes, inflammation, hypertension, cardiovascular disease and reduces metabolic risk factors associated with cancer. Moreover, CR in human beings improves markers of cardiovascular aging, and rejuvenates the skeletal muscle transcriptional profile. More studies are needed to understand the interactions between CR, diet composition, exercise, and other environmental and psychological factors on metabolic and molecular pathways that regulate health and longevity.
    Aging 07/2013; 5(7):507-14. · 6.43 Impact Factor
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    ABSTRACT: Epidemiological and experimental data indicate that diet plays a central role in the pathogenesis of many age-associated chronic diseases, and in the biology of aging itself. Data from several animal studies suggest that the degree and time of calorie restriction (CR) onset, the timing of food intake as well as diet composition, play major roles in promoting health and longevity, breaking the old dogma that only calorie intake is important in extending healthy lifespan. Data from human studies indicate that long-term CR with adequate intake of nutrients results in several metabolic adaptations that reduce the risk of developing type 2 diabetes, hypertension, cardiovascular disease and cancer. Moreover, CR opposes the expected age-associated alterations in myocardial stiffness, autonomic function, and gene expression in the human skeletal muscle. However, it is possible that some of the beneficial effects on metabolic health are not entirely due to CR, but to the high quality diets consumed by the CR practitioners, as suggested by data collected in individuals consuming strict vegan diets. More studies are needed to understand the interactions among single nutrient modifications (e.g. protein/aminoacid, fatty acids, vitamins, phytochemicals, and minerals), the degree of CR and the frequency of food consumption in modulating anti-aging metabolic and molecular pathways, and in the prevention of age-associated diseases.
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    ABSTRACT: To investigate the effects of dietary methionine restriction (MetR) and endurance exercise on bone quality under a condition of estrogen-deficiency, female Sprague Dawley rats (36-week-old) were assigned to a sham surgery group (Sham) or one of five ovariectomized groups subjected to interventions of no treatment (Ovx), endurance exercise (Exe), methionine restriction (MetR), methionine restriction plus endurance exercise (MetR+Exe), and estrogen treatment (Est). Rats in the exercise groups were subjected to a treadmill running regimen. MetR and control diets contained 0.172% and 0.86% methionine, respectively. After the 12-week intervention, all animals were euthanized, and serum and bone tissues were collected for analyses. Compared to estrogen treatment, MetR diet and endurance exercise showed better or equivalent efficiency in reducing body weight gain caused by ovariectomy (p<0.05). While only the Est group showed evidence for reduced bone turnover compared to the Ovx group, MetR diet and/or endurance exercise demonstrated efficiencies in down-regulating serum insulin, leptin, triglyceride and thiobarbituric acid reactive substances (TBARS) (p<0.05). Both the Exe and MetR groups showed higher femoral cortical and total volumetric bone mineral density (vBMD), but only the Exe and Est groups preserved cancellous bone volume and/or vBMD of distal femora (p<0.05) compared to the Ovx group. After being normalized to body mass, femora of the MetR and MetR+Exe groups had relatively higher bending strength and dimension values followed by the Sham, Exe and Est groups (p<0.05). In conclusion, both MetR diet and endurance exercise improved cortical bone properties, but only endurance exercise preserved cancellous bone under estrogen-deficiency. Copyright © 2015, Journal of Applied Physiology.
    Journal of Applied Physiology 07/2015; 119(5):jap.00395.2015. DOI:10.1152/japplphysiol.00395.2015 · 3.06 Impact Factor

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