UNIVERSITY OF CHICAGO, THE
In an ongoing study of aging in free-ranging female rhesus monkeys, we have obtained evidence that chronic stress and repeated activation of the HPA axis in association with low social status and frequent reproduction result in heightened cortisol responses to stress and allostatic load. With this requested supplement, we aim to further characterize allostatic in our aging subjects by conducting post-mortem brain studies. The brain is a major target of stress and allostatic load and long-term exposure to cortisol due to chronic stress accelerates the aging process in areas of the brain that are rich in cortisol receptors. Brain damage resulting from chronic stress and allostatic load can exacerbate the changes in behavior and emotion and the decline in cognitive function that accompany aging. Our study subjects are all the oldest (> 15 years of age) females in the rhesus population (n= 55). It is expected that about 10 of these individuals will die of natural causes within 2 years. With the requested 2-year supplement, we aim to harvest their brains and study them in relation to the physiological and behavioral data we already possess. We will test the hypothesis that aging females who exhibit elevated basal levels of cortisol in feces and elevated plasma cortisol responses to stress and dexamethasone will show evidence of greater neuronal loss and greater loss of synaptic connectivity in the hippocampus, amygdala and prefrontal cortex. We will also investigate the extent to which information about the subject's genotype, family of origin, early social experience, reproductive history, major stressful life events, and detailed behavioral and physiological data collected 1-2 years prior to death can account for variation in brain aging. Because of the many genetic, physiological, and socio-behavioral similarities between rhesus monkeys and humans, the findings of this research can be directly extrapolated to humans and enhance our understanding of the determinants of interindividual variation in aging. The subjects of our current study represent a very valuable research resource; by not taking advantage of the opportunity to study their brains we would miss an important opportunity to gather new knowledge of key biological aspects of the aging process in primates and humans.