Among all female primates, only women are infertile for as much as 30 to 50 % of their lifetimes. One evolutionary theory of aging, the """"""""grandmother hypothesis,"""""""" holds that post-reproductive longevity of women provided a selective advantage because assistance in child-rearing provided by grandmothers led to higher rates of lifetime fertility in their daughters. Humans are also uniquely susceptible to Alzheimer's disease (AD) and its presumed precursor Mild Cognitive Impairment (MCI). We believe that these unique human characteristics, particularly as they occur in women, can best be understood by comparing human's brain and cognitive aging with the same features in our closest relative, the chimpanzee, and in the most widely studied biomedical model of human aging, the rhesus monkey. Accordingly, we propose to study longitudinally cognitive function, emotional processing, brain aging, and of aging in normally aging women, women with AD and MCI, and female rhesus monkeys and chimpanzees. The research program consists of 3 projects. Project 1 will study cognitive and motoric aging in the 3 species and will determine how well classic nonhuman primate tests of cognitive function measure the same capabilities in humans. Project 2 will examine the effects of aging on social cognition and emotional processing in female primates. Project 3 will define the human-specific pattern of brain aging by comparing age-related changes in brain structure in humans, chimpanzees, and macaques, using in vivo imaging and histologic techniques. The projects will be supported by the Administrative and Data Analysis Core, which will have responsibility for storage and analysis of data on a project-wide basis, and by the Animal Core, which will coordinate selection and use of the nonhuman subjects for all projects. The Imaging Core will provide expertise and assistance in collecting and analyzing brain images. Finally, the Reproductive Status Core will monitor subjects'endocrine status during testing. We anticipate that the data will provide new insights into the biological basis of age-related functional decline in female primates, and into the factors that govern successful versus unsuccessful aging. This comparative analysis also can illuminate the origins of human age-related neurodegenerative disorders such as AD, facilitating the development of treatments for this disease.
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