Primates

Caloric restriction (CR), undernutrition without malnutrition, remains the only experimental paradigm that has been shown consistently to extend lifespan and slow aging in short-lived species. Decades of research, mostly in laboratory rodents, have shown that CR consistently extends lifespan, reduces or delays the onset of many age-related diseases and slows aging in many physiological systems. In recent years gerontologists interested in CR have focused on two unanswered questions. 1) What is the relevance of this nutritional paradigm to human aging?

Dietary restriction (DR) delays or prevents age-related diseases and extends lifespan in species ranging from yeast to primates. Although the applicability of this regimen to humans remains uncertain, a proportional response would add more healthy years to the average life than even a cure for cancer or heart disease. Because it is unlikely that many would be willing or able to maintain a DR lifestyle, there has been intense interest in mimicking its beneficial effects on health, and potentially longevity, with drugs.

Human senescence patterns-late onset of mortality increase, slow mortality acceleration, and exceptional longevity-are often described as unique in the animal world.

In most primate groups emigration of the maturing young of one or the other sex tends to serve as an incest avoidance mechanism. Among most primate species it is the males who change groups. This supports the theory that, in terms of reproductive success, males should compete for mates and females should compete for resources. In hominoids the combination of increased longevity and greater female discrimination in mate selection seems responsible for female emigration. This may relate to the high frequency of patrilocality and male control of resources among human groups.

Dietary caloric restriction is the most robust and reproducible means of slowing aging and extending lifespan and healthspan in short-lived mammals and lower organisms. Numerous aspects of this paradigm have been investigated in laboratories around the world since its inception more than 60 years ago. However, two questions about calorie restriction remain unanswered to this day: (1) By what mechanism does it work? and (2) Will it work in humans?

Regression analyses of primate life spans on recently revised female body and brain masses of Old World primates predict a human life span of between 72 years and 91 years-estimates that exceed the age of human menopause (and prior estimates) by well over 20 years. The life spans predicted from body and brain sizes in the early Homo suggest that postreproductive life spans predate Homo sapiens Among anthropoid primates, residual longevity after body and brain effects are controlled is greatest for Homo and for the New World monkeys of the genus Cebus.

Caloric restriction (CR), undernutrition without malnutrition, remains the only experimental paradigm that has been shown consistently to extend lifespan and slow aging in short-lived species. Decades of research, mostly in laboratory rodents, have shown that CR consistently extends lifespan, reduces or delays the onset of many age-related diseases and slows aging in many physiological systems. In recent years gerontologists interested in CR have focused on two unanswered questions. 1) What is the relevance of this nutritional paradigm to human aging?

Dietary caloric restriction (CR) is the only intervention conclusively and reproducibly shown to slow aging and maintain health and vitality in mammals. Although this paradigm has been known for over 60 years, its precise biological mechanisms and applicability to humans remain unknown. We began addressing the latter question in 1987 with the first controlled study of CR in primates (rhesus and squirrel monkeys, which are evolutionarily much closer to humans than the rodents most frequently employed in CR studies).

Calorie restriction increases longevity in rodents, delays the onset of certain diseases and has positive effects on ageing. Studies are ongoing in non-human primates. Eight persons following such a diet for 2 years reacted as anticipated (loss of body weight and fat, decrease in glycaemia and body temperature, etc.). Calorie restriction perhaps teaches us more on the means of resisting malnutrition than on ageing in normal dietary conditions. Calorie restriction is a tool for research, but it should not be recommended by practitioners, notably in elderly patients.

This issue of Biogerontology addresses whether dietary restriction (DR) "...can increase longevity in all species, particularly in human beings". The possibility that DR can increase longevity in all species seems a trivial issue compared to that of DR's potential efficacy in people. The striking phylogenetic breadth of DR's longevity increasing effect supports the notion of human translatability.