The Rhesus Macaque as a Model of Human Aging and Age Related Disease

Mary Ann Ottinger, Julie A. Mattison, Mary B. Zelinski, Julie M. Wu, Steven G. Kohama, George S. Roth, Mark A. Lane, and Donald K. Ingram

The rhesus monkey (Macaca mulatta) offers an advantageous model for biomedical research because of the close relatedness of this species to humans. As in humans, the rhesus monkey experiences deteriorating function of multiple physiological systems during aging, as well as an increasing incidence of pathologies and other health issues. These health issues are generally considered part of "normal" aging. However, there are health problems that arise, which contribute to disease states that become more prevalent in aging populations, such as osteoporosis and metabolic disorders, including diabetes. In addition, the rhesus female provides a valuable experimental model for understanding the biological changes that accompany the process of ovarian aging and the perimenopausal transition, which is an area of high visibility and intense research at this time. Rhesus males also experience age-related increases in health issues despite the fact that they do not have the precipitous hormonal changes seen in females. Moreover, evaluation of cognitive performance and other behavioral changes in rhesus monkeys has proven useful for understanding age-related changes and developing clinically relevant interventions and treatments. Once the elements of the biology and endocrinology of age-related changes are well documented, then there is the opportunity for evaluating other potential interventions that may impact aging processes, including dietary or pharmaceutical regimens. The marked advantage of the rhesus macaque as an experimental model is the similarity and parallel changes to aging in humans. However, this advantage is accompanied by other considerations, including the fact that the rhesus macaque is also long-lived with a lifespan that may be 30-40 years. Therefore, studies utilizing this species for investigating the fundamental biology ofaging require the inclusion of aged animals in the study or sufficient time for a study to be completed, especially for research on the consequences of early exposures or long-term treatments. Nonetheless, the rhesus macaque is unparalleled for obtaining insights into the complexities of aging processes, especially for alterations in cognitive, sensory, and physiologic changes relevant for biomedical applications. In addition, there is growing recognition of the long-term consequences of environmental and health factors on later successful aging as well as the variability among individuals in their lifetime responses. We will provide an overview of the utility of the rhesus macaque as a biomedical model for the study of aging, with emphasis on studies of behavior and on the biology of aging in the female. We will also review some recent research conducted in our laboratories on the potential impact of interventions such as calorie restriction on successful aging.

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