Overview of the NIA Aging Rhesus Monkey Project
Donald K. Ingram, George S. Roth, and Mark A. Lane
Laboratory of Neurosciences, Gerontology Research Center, National. Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD, 21224
With over 70 years of study, the caloric restriction (CR) paradigm has provided gerontology with a unique intervention. Results of numerous rodent studies have demonstrated that CR can slow aging processes manifested as reduced pathology, retained function, and extended lifespan. Although CR studies had been conducted in lower animals, no experiment had been attempted to determine its relevance to human aging prior to 1987. To this end, the National Institute on Aging initiated that year the first CR study in nonhuman primates. Currently about 200 monkeys, mostly rhesus monkeys (Macaca mulatta) with a small number of squirrel monkeys (Saimiri sciureus), aged across their respective lifespans at the time of initiation, have been involved in the study. Control groups receive 2 meals per day sufficient to attain apparent satiety, while the CR group receives 30% less, adjusted for age and body weight. The diet is supplemented with extra micronutrients such that the amount of calories consumed is the only substantive variable manipulated. Results accumulated to date indicate that CR rhesus monkeys are healthier than controls based on the following observations: (1) reduced incidence of various diseases, especially cancer and proliferative diseases; (2) significantly better indices of predisposition to disease, such as lower insulin levels and greater insulin sensitivity, reduced blood lipids and pressure, decreased arterial stiffness, and elevated HDL; and (3) alterations in candidate biomarkers of aging, such as a slower age-related decline in serum dehydroepiandrosterone-sulfate. In addition, CR rhesus monkeys that were juveniles at the onset of the study showed delayed skeletal and sexual maturation, and all CR groups have lower body temperatures than controls. These latter physiological observations are manifestations of a fundamental shift in life history strategy, from growth and reproduction to life maintenance, and appear to reflect adaptations in metabolic and protective gene expression. Although preliminary data suggesting that CR animals exhibit reduced mortality have not yet reached statistical significance, this intervention does appear to exert beneficial effects in primates that suggest a reduced rate of aging. These results offer potential relevance of CR as an anti-aging intervention in humans.
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