Mice and flies and monkeys too: Caloric restriction rejuvenates the aging immune system of non-human primates

Humanity has been obsessed with extending life span and reversing the aging process throughout recorded history and this quest most likely preceded the invention of the written word. The search for eternal youth has spurred holy wars and precipitated the discovery of the new world (the 'Fountain of youth'). It therefore comes as no surprise that an increasingly greater amount of research effort is dedicated to improve our understanding of the aging process and finding interventions to moderate its impact on health. Caloric restriction (CR) is the only intervention in biology that consistently extends maximal and median life span in a variety of short-lived species. Several theories to explain the mechanisms of action of CR have been put forth, including the possibility that CR acts by retarding immune senescence. The question remains, however, whether CR will have the same beneficial impact on human aging, and, if so, how long does CR need to last to produce beneficial effects. To address this question, several groups initiated long-term studies in Rhesus macaques (RM) in the 1980s. Here, we review published data describing the impact of CR on the aging immune system of mice and primates, and discuss our unpublished data that delineate similarities and differences in the effects of CR upon T cell aging and homeostasis between these two models.