Integrative models of aging in the nonhuman primate

Progress in understanding the etiology of human disease and in the development of effective therapies is heavily dependent on appropriate animal models in which to study the underlying causal mechanisms. Because nonhuman primates (NHPs) share many genetic and physiological similarities with humans, they have served as pragmatic models for a wide range of human diseases for several decades. For instance, female rhesus macaques (Macaca mulatta), like women, show ̃28-day menstrual cycles and eventually undergo menopause. In addition, they show many of the same age-related changes in physiological and behavioral functions, including perturbed sleep-wake cycles and cognitive decline. Additional features make NHPs ideal experimental models for aging research. They can be maintained in carefully controlled environments (e.g., photoperiod, temperature, diet, and medication), and self-selection bias that is often unavoidable in human clinical trials can be completely eliminated with NHP studies. The use of NHPs is also advantageous because similar techniques (e.g., activity recording and MRI) can be used to make comparisons between NHPs and humans. In addition, NHPs are out-bred, which enables rigorous validation of research findings that goes beyond the proof of principle provided by rodent models. Finally, because macaques are long-lived species, it is likely that these NHPs have adapted similar maintenance strategies as humans, making them an ideal translational model. Thus, in this chapter we focus on age-related changes in the NHP endocrine, cognitive and immunologic systems, and their contributions to translational research.