The search for an ideal system for elucidating biological changes that accompany aging and relate to processes in humans has led to the development of a variety of invertebrate and vertebrate models. More recently, fundamental processes have been examined across a number of vertebrate classes to determine if these mechanisms occur more generally and if there are some species that show resistance to these age-related challenges that contribute to the demise of the animal. Invertebrates (including Drosophila, nematodes), avian models, and mammalian (rodent) models provide significant contributions to our understanding of aging processes. These models provide essential data that greatly extend the knowledge base to increase understanding of mechanisms of aging. These studies supply the background to facilitate testing of more sophisticated hypotheses. However, the rodent model and other mammalian models do not replace the requirement for subsequent investigations in the nonhuman primate.

In particular, aging is accompanied by increasing incidence of disease and health issues. In some cases, spontaneous disease arises as the physiological condition of the individual worsens. In addition, metabolic and reproductive endocrine systems decline during aging,

Handbook of Models for Human Aging

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resulting in a suite of age-related changes that have global impacts, including altered cognitive function. In particular, female rhesus monkeys experience a true menopause, characterized by the cessation of endometrial sloughing (menstruation). A true menopause is one of the most distinct differences between the nonhuman primate model and other mammalian models. These differences include not only the obvious difference of a lack of a menstrual cycle in rodents, but also differences in neuroendocrine and endocrine events leading to menopause. For example, rodents experience a transitional period of constant estrus, which is associated with declining ovarian function. Although primates also experience a transitional phase in which ovarian function declines with fewer luteal phases, this unopposed estrogen exposure is not as pronounced as in the rodent. In addition, there are a number of high visibility issues associated with the perimenopausal transition that include metabolic, cognitive, and overall health changes. These aspects of the perimenopausal transition require investigations in nonhuman primates, especially relative to development and testing potential interventions for clinical applications.

Therefore, the close relatedness and similarity of physiological systems of the rhesus macaque with humans is a major advantage of this model. In addition, the rhesus monkey has been studied extensively at all stages of the life cycle. This species is considered a long-lived species, with a lifespan of about 1/3 that of humans. However, their long lifespan does present a challenge for researchers because studies on the biology of aging must be long term or utilize retired breeders or other aged individuals. Nonetheless, the complexity of human physiology requires elucidation of fundamental mechanisms operating in the process of aging as well as studies in nonhuman primates to provide definitive data to verify the relevance of these mechanisms to humans.

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