Caloric Restriction in Animals and Non-human Primates
Seventy-five years of research have determined that the longevity and health effects of CR are a broad biological phenomenon that has been observed in species from three kingdoms of life (Animalia, Fungi, and Protoctista).5 Both the mean and maximum life spans of yeast (Saccharomyces cerevisiae), rotifers, nematodes (Caenorhabditis elegans), fruit flies (Drosophila melanogaster) and medflies, spiders, fish (guppies, zebrafish), rodents (hamsters, rats, mice), and dogs have been extended significantly by decreasing normal caloric consumption by 30‒40%.6 Recently, the effects of CR on lifespan have been observed in non-human primates. The rhesus monkey (Macaca mulatta) is an excellent model for the study of human aging, exhibiting many physiological and biochemical similarities to humans.7 Unlike other animal aging models, the rhesus monkey also allows the study of brain atrophy, a characteristic of human aging that does not occur in smaller mammals.8 With an average lifespan of about 27 years in captivity,9 the rhesus also is suitable for determining the effects of CR on maximal lifespan.
Studies of the effects of CR on three separate rhesus colonies are currently underway; results from two have been published. A 20-year study conducted at the Wisconsin National Primate Research Center suggests that CR of baseline diet by 30% may slow aging in the rhesus, as gauged by two indicators of aging retardation: delays in mortality, and in the onset of age-associated diseases (particularly diabetes, cancer, cardiovascular disease, and neurological impairment; the most prevalent age-related diseases in humans).10 At study entry, the animals (46 males and 30 females) were at adult age (7‒14 years); at the time the study was published (twenty years later), nearly three times as many control monkeys had died of age-related causes than CR monkeys (37% vs. 13%). The CR monkeys appeared to be biologically younger than their normal-fed counterparts, and not surprisingly, had lower body and fat mass. Sarcopenia (age-related muscle loss) was attenuated in the CR group. CR monkeys were also free of diabetes (compared to 5/38 of control animals) or glucose intolerance (compared to 11/38 of control animals). Incidence of cardiovascular disease, all cancers, and adenocarcinoma of the GI tract (the most common cancer in rhesus monkeys)11 was reduced by half in the CR group. Calorie restriction resulted in preservation of brain volume in the caudate, putamen and insula, areas that are classically involved in regulation of motor and executive function. The effects of CR on maximum lifespan have yet to be determined for this colony, as animals in both groups are still living.
A smaller study at the University of Maryland tracked eight CR rhesus monkeys and 109 ad-libitum (free-fed) controls over a period of 25 years, and produced many of the same observations.12,13 Ad libitum fed animals died at 25 years of age compared to a median survival of 32 years in the CR group. Calorie restriction also reduced hyperinsulinemia (elevated circulating insulin) and the frequency of age-associated diseases.
Although the available data is limited, these two studies do implicate that the healthspan and lifespan benefits of CR that have been observed in rodents and lower animals may also extend to primates and possibly man.