Dietary Restriction in Aging Nonhuman Primates

Abstract

Dietary restriction (DR) has been shown to benefit health and longevity in a wide variety of species, although most have maximal life spans of only a few years. In 1987, the National Institute on Aging began the first well-controlled long-term study in a species with a considerably longer life span and a closer physiology to humans. Using rhesus monkeys (Macaca mulatta), an extensive array of physiological measures have been conducted in both males and females to evaluate the effects of DR. Monkeys benefit from DR with a lower body weight, body fat, blood glucose and thus are at lower risk for developing diabetes. Changes in several endocrine measures indicate an altered hormonal axis; however, circadian patterns and timing relative to the onset of DR can obscure the differences. Despite the caloric deficit, female monkeys are not reproductively compromised, and both males and females may benefit immunologically. There remains much to be learned from this model of DR including whether long-term DR will increase life span in a primate species.

Insulin Signaling and Insulin Sensitizing in Muscle and Liver of Obese Monkeys: Peroxisome Proliferator-Activated Receptor Gamma Agonist Improves Defective Activation of Atypical Protein Kinase C

“…Calorie restriction and calorie restriction mimetic agents have been demonstrated in rhesus monkeys to reverse or prevent these metabolic disorders (13,21,24,42,45,46,50,60,64). From previous findings in obese insulin-resistant monkeys (55,57,61,76) and the present study, it seems clear that, whereas insulin signaling to IRS-1-dependent PI3K, PKB, aPKC, and GS is compromised in muscle of obese monkeys…”

“…These diseases of aging are very similar in humans and in rhesus monkeys; the middle-aged onset of metabolic syndrome includes obesity, dyslipidemia, and impaired glucose tolerance, often progressing to overt type 2 diabetes mellitus (8, 9, 21-23, 32, 33, 67). Rhesus monkeys and humans have highly similar metabolism (17,42,46,68) and genomic features (20,50). Diabetes and insulin resistance in monkeys and other non-human primates are likely to have the same mechanistic causes as underlie diabetes development in overweight middle-aged humans (11).…”

Nutrition, Brain Aging, and Neurodegeneration: Table 1.

“…A␤ deposition in squirrel monkeys on a CR regimen is also reduced (Qin et al, 2006a). Similarly long-term studies of rhesus monkeys conducted at the National Institute on Aging and the University of Wisconsin have produced data indicating that CR animals (30% less than controls) are healthier than fully fed counterparts based on reduced incidence of various diseases, on exhibition of better indices of predisposition to disease, and slower rates of aging based on analysis of several biomarkers (Ramsey et al, 2000;Roth et al, 2004;Mattison et al, 2007;Raman et al, 2007). A recent report also indicates a significant increase in survival in CR monkeys as well as attenuation of the age-related declines in brain volume in selected regions .…”

“Control” laboratory rodents are metabolically morbid: Why it matters

“…In both cases the animals are fed portioned meals two or three times daily and may exercise in large cages or open arenas; accordingly, they maintain lower levels of body fat compared to laboratory rats and mice. In contrast to rodents whose lifespans are shortened by the usual housing conditions, the lifespans of dogs (10-20 years for beagles) and monkeys (25-40 years for rhesus macaques) are believed similar to their wild counterparts (96,97). On the other hand, some organ systems of dogs and monkeys are more sensitive than their rodent counterparts to adverse effects of excessive energy intake, with the cardiovascular system being one clear example, where rodents are resistant to atherosclerosis.…”