Guest guest Posted February 11, 2007 Report Share Posted February 11, 2007 Rhesus monkey CR is described, as of 1997. The below pdf-availed paper is not described for its abstract and citation in Medline. Beyond the rodent model: Calorie restriction in rhesus monkeys Authors Mark A. Lane, K. Ingram and S. Roth Age, Vol. 20, 29-44, 1997 Text PDF (1,515 kb) ABSTRACT Lifespan extension and reduction of age-related disease by calorie restriction (CR) are among the most consistent findings in gerontological research. The well known effects of CR have been demonstrated many times in rodents and other short-lived species. However, effects of CR on aging in longer-lived species, more closely related to humans, were unknown until recently. Studies of CR and aging using nonhuman primates (rhesus monkeys) were begun several years ago at the National Institute on Aging, the University of Wisconsin-Madison, and the University of land. These studies are beginning to yield useful data regarding the effects of this nutritional intervention in primates. Several studies from these ongoing investigations have shown that rhesus monkeys on CR exhibit physiological responses to CR that parallel findings in rodents. In addition, several potential biomarkers of aging are being evaluated and preliminary findings suggest the possibility that CR in rhesus monkeys could slow the rate of aging and reduce age-related disease, specifically diabetes and cardiovascular disease. It will be several years before conclusive proof that CR slows aging and extends life span in primates is established, however, results from these exciting studies suggest the possibility that the anti-aging effects of CR reported in rodents also occur in longer-lived species such as nonhuman primates, strengthening the possibility that this nutritional intervention will also prove beneficial in longer-lived species, including humans. Table 1. Calorie restriction.studies in rhesus monkeys. =========================================================== NIA Univ. of Wisc. Univ. of Md. =========================================================== Age Range (initiation of CR) 1-2, 3-5, > 15 8-14 11-12 Sex (n) Long-term M (60), F (60) M (30), F (30) M (16-27)^a Mechanistic studies M (28), F (12) M (16) Total 160 76 27 Diet Semi-synthetic Synthetic Purina Chow/Ensure Fat % 5% 10% 13% (chow), 31% (Ensure)^b Supplement yes (premix) yes (premix)^c yes (chewable vitamin) CR paradigm Thirty % of control level^d Thirty % of baseline individual intake Weight stabilization =========================================================== a The exact number of control animals varies between 8-19 dependent on the experiment, 8 monkeys have been on long-term CR. b Three control monkeys receive Ensure diet. c Supplement has been given since 1994. d Control allotments based on NRC Guidelines. Food consumption studies over the course of the study have shown this to approximate ad libitum consumption. Table 2. Effects of CR on body composition and development. ======================================================== Study Group Body Weight Body Fat Lean Mass Maturation ======================================================== NIA Decreased Decreased Decreased Delayed sexual and skeletal U.W. Delayed skeletal Delayed skeletal - U.Md. Decreased Decreased - - Table 3. Glucoregulatory changes in rhesus monkeys subjected to CR. ================================================= Study Fasting glucose Fasting insulin Insulin sensitivity Glucose disappearance (K[c]) ================================================= NIA Decreased Decreased unchanged U.W. Decreased Decreased Increased Unchanged U.Md. Unchanged Decreased Decreased Increased ================================================= SUMMARY Calorie restriction is the only non-genetic intervention which consistently extends life span and slows the rate of aging in short-lived mammals. Over the past several decades extensive literature on CR in rodents has evolved, however, until recently, little was known about effects of CR in longer-lived species more closely related to humans. In the last 5 years there has been a significant increase in published reports regarding the effects of CR in nonhuman primates. One of the most important conclusions to emerge from these studies is that physiologically, rodents and monkeys on CR respond in a similar manner. A summary comparing findings between rodent and rhesus monkeys on CR is presented in Table 4. Table 4. Comparison of CR effects in rodents and monkeys ============================================== Finding Rodents Monkeys ============================================== Body Composition body weight Decreased Decreased body fat Decreased Decreased lean mass Decreased Decreased Development/maturation sexual Decreased Decreased skeletal Decreased Decreased Metabolism fasting glucose Decreased Decreased fasting insulin Decreased Decreased insulin sensitivity Decreased Decreased energy expenditure (long-term) No difference No difference energy expenditure (short-term) Decreased Decreased body temperature Decreased Decreased locomotor activity Decreased No change Lipids/lipoproteins trigtycerides Decreased Decreased HDL(2b) ? Increased Biomarkers/other effects wound closure No change/slowed No change clonal efficiency ? Increased DHEAS ? Delayed decline IL-6 Decreased Decreased IGF-1 Decreased Decreased The growing body of evidence from the monkey studies show that CR induces a wide variety of changes in physiological function that are consistent with data reported in rodent studies in which life span has been extended. Furthermore, it is interesting to note that many of these findings, such as reduced glucose and insulin, effects on 24-h EE, and reduced body temperature, are consistent with physiological changes that have been proposed as related to possible mechanisms of CR in rodents. This universality across species could be interpreted as evidence that metabolic changes of this sort represent " fundamental " responses to CR and suggest the importance of metabolism in the search for possible mechanisms of the anti-aging and anti-disease effects of CR. It will be several more years before it is known if CR significantly extends life span in longer-lived species, however, several biomarkers of aging have been identified and preliminary findings suggest that CR might affect the rate of aging in rhesus monkeys. The findings to date from studies of CR in rhesus monkeys strengthen the possibility that CR will extend life span and slow aging in longer-lived mammals. It is apparent from the monkey studies that even if the marked extension of life span associated with CR in rodents does not occur in monkeys, this nutritional intervention will reduce or delay the onset of several age-related diseases, such as diabetes and cardiovascular disease, thus improving the quality of life in later years. -- Al Pater, alpater@... -- Al Pater, PhD; email: Alpater@... ________________________________________________________________________________\ ____ Now that's room service! 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