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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1-ZIJ-9 (O1))
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Wagster, Molly V
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Emory University
Other Domestic Higher Education
United States
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Bruner, Emiliano; Preuss, Todd M; Chen, Xu et al. (2017) Evidence for expansion of the precuneus in human evolution. Brain Struct Funct 222:1053-1060
Hecht, E E; Mahovetz, L M; Preuss, T M et al. (2017) A neuroanatomical predictor of mirror self-recognition in chimpanzees. Soc Cogn Affect Neurosci 12:37-48
Pereira-Pedro, Ana Sofia; Rilling, James K; Chen, Xu et al. (2017) Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary Expansion of the Human Precuneus. Brain Behav Evol 90:255-263
Donahue, Chad J; Sotiropoulos, Stamatios N; Jbabdi, Saad et al. (2016) Using Diffusion Tractography to Predict Cortical Connection Strength and Distance: A Quantitative Comparison with Tracers in the Monkey. J Neurosci 36:6758-70
Rosen, Rebecca F; Tomidokoro, Yasushi; Farberg, Aaron S et al. (2016) Comparative pathobiology of ?-amyloid and the unique susceptibility of humans to Alzheimer's disease. Neurobiol Aging 44:185-196
van den Heuvel, Martijn P; de Reus, Marcel A; Feldman Barrett, Lisa et al. (2015) Comparison of diffusion tractography and tract-tracing measures of connectivity strength in rhesus macaque connectome. Hum Brain Mapp 36:3064-75
Hecht, Erin E; Gutman, David A; Bradley, Bruce A et al. (2015) Virtual dissection and comparative connectivity of the superior longitudinal fasciculus in chimpanzees and humans. Neuroimage 108:124-37
Bloomsmith, Mollie; Neu, Kim; Franklin, Andrea et al. (2015) Positive reinforcement methods to train chimpanzees to cooperate with urine collection. J Am Assoc Lab Anim Sci 54:66-9
Zhang, Tuo; Chen, Hanbo; Guo, Lei et al. (2014) Characterization of U-shape streamline fibers: Methods and applications. Med Image Anal 18:795-807
Autrey, Michelle M; Reamer, Lisa A; Mareno, Mary Catherine et al. (2014) Age-related effects in the neocortical organization of chimpanzees: gray and white matter volume, cortical thickness, and gyrification. Neuroimage 101:59-67

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