Evolution of Aging and Dementia in Female Primates

描述（由申请人提供）：在所有雌性灵长类动物中，只有女性在其一生中有30%至50%的时间是不育的。一种关于衰老的进化理论——“祖母假说”认为，女性在生育后的长寿提供了一种选择优势，因为祖母在抚养孩子方面提供的帮助导致了她们女儿的终生生育率更高。人类也特别容易患阿尔茨海默病（AD）及其假定的前兆轻度认知障碍（MCI）。我们相信，这些独特的人类特征，尤其是发生在女性身上的特征，可以通过将人类的大脑和认知衰老与我们最近的亲戚黑猩猩以及研究最广泛的人类衰老生物医学模型恒河猴的相同特征进行比较来最好地理解。因此，我们建议纵向研究正常衰老女性、患有AD和MCI的女性、雌性恒河猴和黑猩猩的认知功能、情绪加工、大脑衰老和衰老。研究计划包括3个项目。项目1将研究这三个物种的认知和运动老化，并确定经典的非人类灵长类动物认知功能测试在人类身上的效果如何。项目二将研究衰老对雌性灵长类动物社会认知和情绪处理的影响。项目3将使用活体成像和组织学技术，通过比较人类、黑猩猩和猕猴的大脑结构与年龄相关的变化，来定义人类特有的大脑衰老模式。这些项目将由行政和数据分析中心（Administrative and Data Analysis Core）和动物中心（Animal Core）提供支持，前者将负责整个项目范围内数据的存储和分析，后者将协调所有项目中非人类受试者的选择和使用。成像核心将在收集和分析大脑图像方面提供专业知识和协助。最后，生殖状态核心将在测试期间监测受试者的内分泌状态。我们预计这些数据将为女性灵长类动物与年龄相关的功能衰退的生物学基础以及控制成功与不成功衰老的因素提供新的见解。这种比较分析也可以阐明人类与年龄相关的神经退行性疾病（如AD）的起源，促进这种疾病治疗方法的发展。

DESCRIPTION (provided by applicant): 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.