Determinants of Human Longevity and Healthy Aging

描述(申请人提供)：我们的人口正在老龄化，最大的增长发生在85岁及以上的年龄段。这种人口结构趋势使现有的医疗保健和社会保障结构处于危险之中。我们的目标是提供基本知识，以便创建预防性和补偿性干预措施，以改善老年人的功能状况，从而防止养老院人口的急剧增长。遗传因素和环境因素都对老年人的衰老和生活质量起着作用。我们将确定一个人的能量代谢特征，这些特征有利于长寿和保持身体和认知能力，促进与健康老龄化相关的幸福感。这将通过在遗传、分子、细胞和生理水平上检查代谢因素，并通过仔细检查非老年和年轻受试者的环境影响来完成。群体遗传学方法将被应用于与新陈代谢和抗逆性有关的候选基因。这将与葡萄糖调节基因表达的全球图谱分析以及T细胞功能的检查相结合。身体成分、静息代谢率和自由生活能量消耗测定，以及氧化应激评估，将提供生理参数。身体机能将通过体检、日常生活能力(ADL)调查和基于ADL的体能测试进行评估。认知能力将通过检查个体在一般智力能力和情景记忆方面的差异来确定。人口、家庭、医疗和生活方式等因素将有助于我们的分析。试点干预也将是我们调查的一部分。这些研究将在五个项目中进行，这些项目将由一个行政核心提供支助，其中包括医疗评估股；一个抽样和数据管理核心，该核心将提供统计支助并维护一个中央、安全的网上数据库；以及一个征聘和临床测试核心，该核心将运作一个一站式中央测试设施。该研究计划是跨学科的，跨越了遗传学和分子，从生理到生理功能和心理。我们的目的是为老年人口功能和残疾的多领域建模提供基础。拟议的研究对衰老、肌肉骨骼和传染病以及糖尿病和精神健康具有重要影响。

DESCRIPTION (provided by applicant): Our population is growing older, and the greatest increases are occurring in the 85 and older age group. This demographic trend places in jeopardy the existing structures for healthcare delivery and social security. Our goal is to provide the fundamental knowledge that will allow the creation of preventive and compensatory interventions to improve the functional status of our seniors and thus to prevent a dramatic expansion of the nursing home population. Both genetic and environmental factors play a role in aging and the quality of life in the elderly. We will identify characteristics of an individual's energy metabolism that predispose to long life and retention of physical and cognitive capacity, promoting the sense of well being associated with healthy aging. This will be done by examining metabolic factors at the genetic, molecular, cellular, and physiologic levels, and by scrutinizing environmental influences in nonagenarians and younger subjects. Population genetic methods will be applied to candidate genes implicated in metabolism and stress resistance. This will be coupled to the analysis of global profiles of glucose-regulated gene expression in conjunction with an examination of T cell function. Body composition, resting metabolic rate, and free-living energy expenditure determinations, as well as assessment of oxidative stress, will provide the physiologic parameters. Physical function will be assessed by physical examination, activity of daily living (ADL) surveys, and ADL-based tests of physical fitness. Cognitive capacity will be ascertained by examination of individual differences in general intellectual abilities and of episodic memory. Demographic, familial, medical, and lifestyle factors will contribute to our analysis. Pilot interventions will also be part of our investigation. These studies will be carried out in five Projects, which will be supported by an Administrative Core, housing the Medical Assessment Unit, a Sampling and Data Management Core, which will provide statistical support and maintain a central, secure, web-based database, and a Recruitment and Clinical Testing Core, which will operate a one-stop, central testing facility. The research program is interdisciplinary, spanning the genetic and molecular through the physiologic to physical function and psychology. Our purpose is to provide the bases for multi-domain modeling of function and disablement in the elderly population. The proposed studies have important implications for aging, musculoskeletal and infectious diseases, as well as diabetes and mental health.