The Human Life Course and the Biodemography of Aging

描述（由申请人提供）：拟议的更新有三个总体目标：a)利用进一步的现代方法和个人纵向数据，详细记录生活在前现代背景下的采食园艺社会Tsimane的生物学，流行病学和衰老行为，以及它如何随着文化适应而变化；b)检验由于传染病负担沉重和能量平衡不平衡，提斯曼人相对于发达国家的人衰老速度加快的假设；c)评估pi在其研究计划过程中开发的人类生活史和衰老的特定理论。为了实现这些目标，这次竞争性复兴有三个具体目标。目的1是获得40岁以后身体和认知功能、能量产生、发病率、合并症、死亡率和社会角色的纵向抽样。目的2是确定免疫系统获得性臂和先天臂的免疫衰老率。目的3是确定血管、心脏和肾脏疾病的发病率及其相关病因过程。该项目的继续将使我们能够建立一个跨越成人年龄范围的大样本的纵向剖面，并模拟感染，营养，器官功能和损伤，以及在前现代，高度传染性环境中达到成熟的人群的身体和认知功能之间的相互作用。对于这四个具体目标中的每一个，我们都将把我们的结果与在美国和其他国家获得的结果进行比较，并在提斯曼人口中建立个体差异模型。我们还将评估社区和个人层面文化适应的群体内差异对这些结果变量的影响。在此过程中，我们将模拟不断变化的经济活动、住房条件、医疗设施的使用、西班牙语能力和识字率的影响，并将其与健康、身体和认知状况以及死亡率的数据联系起来。感染和预期寿命或死亡率的发展梯度将为探索进化假设和探索感染、炎症和衰老病理生理之间关系的细节提供进一步的数据。

DESCRIPTION (provided by applicant):There are three overarching goals for the proposed renewal: a) further document in detail the biology, epidemiology and behavior of aging among the Tsimane, a forager-horticultural society living in a pre-modern context, and how it changes with acculturation, utilizing further modern methodologies and individual longitudinal data; b) test the hypothesis that aging among the Tsimane is accelerated relative to people in developed nations due to the heavy burden of infectious disease and low energy balance; and c) evaluate a specific theory of human life history and aging developed by the PIs during the course of their research program. To accomplish these goals, there are three specific aims of this competitive renewal. Aim 1 is to obtain longitudinal sampling of physical and cognitive function, energy production, morbidity, co- morbidity, mortality, and social roles after age 40. Aim 2 is to determine rates of immunosenescence for both the acquired and innate arms of the immune system. Aim 3 is to determine rates of vascular, heart and kidney disease, and their associated etiological processes. The continuation of this project will allow us to build a longitudinal profile of a large sample of persons who span the adult age range and to model interactions between infection, nutrition, organ functioning and damage, and physical and cognitive functioning in a population that reached maturity in a pre-modern, highly infectious environment. For each of the four specific aims, we will both compare our results to those obtained in the U.S. and other countries, and model individual variation within the Tsimane population. We will also assess the effects of the within-population variance in acculturation at both the community and individual levels on those outcome variables. In so doing, we will model the effects of changing economic activities, housing conditions, use of medical facilities, Spanish competency, and literacy, and link them to data on health, physical and cognitive status, and mortality. The developing gradients of infection and life expectancy or mortality will provide further data to explore evolutionary hypotheses and to explore the details of the relationships between infection, inflammation and the pathophysiology of aging. PUBLIC HEALTH RELEVANCE: This renewal will provide detailed information on the impacts of infectious disease on health, functional status and mortality in a pre-modern population of forager-horticulturalists of South America experiencing similar demographic conditions as those in mid-19th century Europe. Investigation of arterial, heart and kidney disease in a large sample of older adults can reveal unique insights about the relative contributions of diet, energy expenditure and inflammation due to disease on the rate of physiological aging. In all societies including the contemporary American experience. The results, combined with measures of aging and disease in other populations such as the U.S., Mexico and Indonesia, may help to explain the historical increases in life expectancy over the past several centuries.