Preparation of Samples for Investigation of Biological Aging among the Tsimane

申请者描述(申请人提供)：本申请申请资金，用于准备和化验收集的生物样本，以便为随后调查玻利维亚齐曼人从幼年到老年的感染、炎症、免疫功能、代谢指标、激素水平、遗传因素以及其他生理过程和健康结果的指标之间的联系做准备。使用低预期寿命人群的数据和反映一个多世纪前美国和欧洲经历的历史条件的流行病学环境的数据，将使我们能够横向阅读历史，并评估将环境条件与广泛的综合生理系统的生物过程联系起来的假设。这项研究的一个广泛目的是推进关于人类生命过程的生物人口学理论，特别是关于衰老和寿命的理论。这项研究的生物学理论将衰老与营养和炎症之间的协同作用以及它们在氧化应激、躯体修复和生长中的作用联系起来。被研究的人群提供了机会来检验经验性证据，这些证据阐述了与高度传染性环境中人类寿命演变相关的能量分配策略相关的理论。Tsimane的数据来自一项正在进行的多波人类学研究，该研究收集了未经分析的血清、血浆、白细胞和尿液的冰冻样本。初步分析表明，有能力收集、实地储存和运输生物样本。其中一些冷冻样本自2004年以来一直在储存，在它们降解之前需要进行检测。生物样本将从大约1700人中进行化验，其中约400人年龄在40岁以上。其中一些分析将在所有年龄段进行，并且只进行一次，例如遗传标记，以表明特定年龄群体的标记水平。其他化验将根据年龄进行，一些化验将从同一人在多个时间点收集的样本中进行。这通常适用于40岁及以上的样本，以检查个体在标记中的稳定性(通常在3个时间点)，检查随年龄的变化(超过4年的时间)，并将一个生物指标随时间的变化与其他生物指标的变化或其他生理、人口和环境条件的变化联系起来。在这个项目中产生的指标将使我们能够测试关于生理资源在独特的流行病学环境中对生长和修复、活动和生殖的分配的新假说。该项目在许多方面都是探索性的：环境在流行病学条件下是独一无二的；一些检测方法被用来确定这个或任何其他人群所不熟悉的全年龄段的生物学特征；少数检测方法在这个人群中是探索性的；将用这些检测方法提供的数据进行测试的理论模型将大大增加我们对过去、现在和未来生理衰老的理解。与公共卫生相关：拟议的项目将提供信息，以更好地了解我们进化的世界，一个感染和营养资源稀缺的世界。利用该项目产生的数据开展的工作将使我们能够评估现代世界的条件如何可能导致人口老龄化的不利条件，如肥胖和营养过剩。现代世界几乎没有感染，资源丰富。这一项目的结果将使我们更好地理解全世界一生中感染率下降在导致晚年衰老速度变化中的作用。

DESCRIPTION (provided by applicant): This application requests funds for the preparation and assay of collected biological samples in order to prepare for subsequent investigation of the links between infection, inflammation, immune function, metabolic indicators, hormonal levels, genetic factors, and indicators of additional physiological processes and health outcomes from early childhood through old age among the Tsimane of Bolivia. The use of data for a population with a low life expectancy and an epidemiological environment reflecting historical conditions experienced in the United States and Europe more than a century ago will allow us to read history sideways and evaluate hypotheses relating environmental conditions to biological processes across a broad set of integrated physiological systems. A broad aim of this investigation is to advance theory on the biodemography of the human life course, with a specific focus on aging and the lifespan. The biological theory underlying this investigation links aging to synergies between nutrition and inflammation and their role in oxidative stress, somatic repair and growth. The population studied provides the opportunity to examine empirical evidence that addresses theories linking energy allocation strategies relevant to the evolution of the human lifespan in a highly infectious environment. Data for the Tsimane come from an ongoing multiwave anthropological study that has collected unanalyzed frozen samples of blood serum, plasma, leukocytes, and urine. Pilot analysis has indicated ability to collect, store in the field, and transport biological samples. Some of these frozen samples have been stored since 2004 and there is a need for assay before they degrade. Biological samples will be assayed from approximately 1700 individuals, about 400 of whom are over the age of 40. Some of these assays will be done across all ages and only one time, e.g. genetic markers, to indicate age-specific population levels of markers. Other assays will be age-specific and some will be done from samples collected from the same individuals at multiple time points. These will generally be for the sample 40 years of age and over to examine individual stability in the marker (generally at 3 time points), to examine change with age (over 4 years of time), and to link change over time in one biological indicator to changes in others or to other physiological, demographic and environmental conditions. The indicators produced in this project will allow us to test novel hypotheses about the distribution of physiological resources to growth and repair, activity, and reproduction in a unique epidemiological setting. The project is exploratory in a number of ways: the setting is unique in its epidemiological conditions; some of the assays are used to identify biological characteristics across the full range of ages which is not well-known for this or any other population; a small number of the assays are exploratory in this population; the theoretical models that will be tested with the data provided by these assays will add significantly to our understanding of past, current, and future physiological aging. PUBLIC HEALTH RELEVANCE: The proposed project will provide information to better understand the world in which we evolved, a world of infection and scarce nutrition resources. The work carried out with the data produced through this project will allow us to assess how conditions in the modern world, with little exposure to infection and extensive resources, may result in adverse conditions for an aging population such as obesity and overnutrition. Results of this project will lead us to better understand the role of worldwide declines in infection throughout life in causing changes in the rate of aging in later life.