The aged female rhesus macaque as a translational model for human menopause and hormone therapy

Abstract

Progress in understanding the causes of physiological and behavioral changes in post-menopausal women is hampered by the paucity of animal models that accurately recapitulate these age-associated changes. Here we evaluate the translational potential of female rhesus macaques (Macaca mulatta). Like women, these long-lived diurnal primates show marked neuroendocrine changes during aging, as well as perturbed sleep-wake cycles and cognitive decline. Furthermore, the brains of old rhesus macaques show some of the same pathological hallmarks of Alzheimer's disease as do humans, including amyloidosis and tauopathology. Importantly, unlike humans, rhesus macaques can be maintained under tightly controlled environmental conditions, such as photoperiod, temperature and diet, and tissues can be collected with zero postmortem interval; this makes them especially suitable for studies aimed at elucidating underlying molecular mechanisms. Recent findings from female macaques are helping to elucidate how sex-steroids influence gene expression within the brain and contribute to the maintenance of cognitive function and amelioration of age-associated pathologies. Taken together, these findings emphasize the translational value of female rhesus macaques as a model for elucidating causal mechanisms that underlie normative and pathological changes in post-menopausal women. They also provide a pragmatic platform upon which to develop safe and effective therapies.