Evolution of Aging and Dementia in Female Primates

雌性灵长类动物衰老和痴呆的进化

• 批准号: 7184570
• 负责人: JAMES G HERNDON
• 金额: $ 208.24万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-15 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7184570
• 关键词: Evolution; Aging; Dementia; Female; Primates

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.

描述（由申请人提供）：在所有雌性灵长类动物中，只有雌性在其一生的 30% 至 50% 的时间内不生育。一种关于衰老的进化理论，即“祖母假说”，认为女性的生育后长寿提供了一种选择性优势，因为祖母提供的育儿帮助导致了女儿终生生育率的提高。人类还特别容易罹患阿尔茨海默病 (AD) 及其假定的前体轻度认知障碍 (MCI)。我们相信，这些独特的人类特征，特别是在女性身上出现的特征，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 的女性以及雌性恒河猴和黑猩猩的认知功能、情绪处理、大脑衰老和衰老过程。该研究计划由3个项目组成。项目 1 将研究这 3 个物种的认知和运动衰老，并将确定经典的非人类灵长类认知功能测试如何衡量人类的相同能力。项目 2 将研究衰老对雌性灵长类动物社会认知和情感处理的影响。项目 3 将利用体内成像和组织学技术，比较人类、黑猩猩和猕猴的大脑结构与年龄相关的变化，从而定义人类特有的大脑衰老模式。这些项目将得到管理和数据分析核心的支持，该核心将负责整个项目范围内数据的存储和分析，以及动物核心的支持，后者将协调所有项目非人类受试者的选择和使用。成像核心将提供收集和分析大脑图像的专业知识和帮助。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雌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。这种比较分析还可以阐明人类与年龄相关的神经退行性疾病（例如 AD）的起源，从而促进该疾病治疗方法的开发。