Evolution of Aging and Dementia in Female Primates

描述(申请人提供)：在所有女性灵长类动物中，只有女性在其一生中有30%到50%的时间是不育的。一种关于衰老的进化论，即“祖母假说”认为，女性生育后的长寿提供了一种选择性优势，因为祖母在育儿方面提供的帮助会导致她们的女儿终身生育率更高。人类还特别容易患阿尔茨海默病(AD)及其推测的前驱轻度认知障碍(MCI)。我们认为，这些独特的人类特征，特别是发生在女性身上的特征，最好的理解方法是将人类的大脑和认知老化与我们的近亲黑猩猩和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。因此，我们建议研究正常衰老女性、患有AD和MCI的女性以及雌性恒河猴和黑猩猩的纵向认知功能、情绪处理、脑老化和衰老。该研究计划由3个项目组成。项目一将研究这三个物种的认知和运动衰老，并将确定经典的非人类灵长类动物认知功能测试在人类中衡量相同能力的程度。项目2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、黑猩猩和猕猴大脑结构中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核心和动物核心提供支助，前者负责在整个项目基础上存储和分析数据，后者将协调为所有项目选择和使用非人类受试者。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，生殖状态核心将监测受试者在测试期间的内分泌状态。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，以及决定成功和不成功衰老的因素提供新的见解。这种比较分析还可以阐明人类年龄相关神经退行性疾病的起源，如阿尔茨海默病，有助于开发这种疾病的治疗方法。

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.