Human Life Course and the Biodemography of Aging

 描述（由申请人提供）：该项目将测试关于传染病和炎症对心血管疾病和糖尿病影响的替代模型。对玻利维亚的Tsimane觅食园艺家进行了十多年的研究，发现由于多种感染过程，一生中炎症的发生率很高。鉴于炎症是动脉粥样硬化的病因，并预测心肌梗死和中风的风险，令人惊讶的是，我们在Tsimane中发现了轻微的高血压，几乎没有梗死，相对于年龄匹配的西方人，舒张功能改善，糖尿病发病率低，血脂水平低，特别是LDL。该项目将综合10多年的面板数据，以解决为什么Tsimane心血管功能保持良好，以及为什么糖尿病风险在整个成年期保持较低。R01更新申请有三个具体目标。目标1完成对过去十年收集的储存生物标本（血清、尿液、粪便）和心血管数据（如超声检查、眼压测量）的分析。目的2利用家系资料对心脏代谢和免疫相关性状进行遗传力分析，控制遗传变异的影响，并评估这些性状是否具有共同的影响。目的3检验来自感染、免疫调节、心血管疾病和糖尿病的替代模型的假设，其中包括检查生活方式因素（例如饮食、体力活动水平）、遗传性及其相互作用的相对重要性。Tsimane提供了一个独特的机会，可以研究工业化前人口的动脉，心脏和代谢健康，这些人口具有高感染负荷，但一生中食物摄入量有限，身体活动量大。我们将采用与其他国家采用的方法直接可比的综合纵向流行病学，人口统计学和人类学方法，包括测量免疫反应（体内和体外），组织学，超声成像和动脉张力测定。我们还将能够检查文化适应对传染性和非传染性疾病过程的影响，在社区，家庭和个人层面。我们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，以评估感染、炎症、生活方式和遗传性对整个生命过程中心血管和代谢健康的相对影响。

 DESCRIPTION (provided by applicant): This project will test alternative models regarding the impacts of infectious disease and inflammation on cardiovascular disease and diabetes. Over a decade of research on Tsimane forager-horticulturalists of Bolivia has revealed high rates of inflammation throughout life due to multiple infectious processes. Given that inflammation is causally involved in atherosclerosis and predicts risk of myocardial infarction and stroke, it is striking that we find among Tsimane minimal hypertension, a near absence of infarcts, improved diastolic function relative to age-matched Westerners, low incidence of diabetes, and low serum lipid levels, particularly LDLs. This project will synthesize 10+ years of panel data to address why Tsimane cardiovascular function remains well-preserved and why diabetes risk remains low throughout adulthood. There are three specific aims of this R01 renewal application. Aim 1 completes analyses of stored biological specimens (serum, urine, feces) and cardiovascular data (e.g. ultrasonographic, tonometric) collected over the last decade. Aim 2 conducts heritability analyses on cardiometabolic and immune-related traits using genealogically derived pedigrees, to control for effects of heritable variation and to assess whether these traits share common influences. Aim 3 tests hypotheses derived from alternative models of infection, immune regulation, cardiovascular disease and diabetes, which include examining the relative importance of lifestyle factors (e.g. diet, physical activity level), heritability and their interations. The Tsimane provide a unique opportunity to study arterial, heart and metabolic health in a pre-industrial population with high infectious load but with limited food intake and high physical activity throughout life. We will employ integrated longitudinal epidemiological, demographic and anthropological methodologies that are directly comparable to methods employed in other countries, including measurement of immune responses (in vivo and in vitro), histology, ultrasound imaging, and arterial tonometry. We will also be able to examine effects of acculturation on communicable and non-communicable disease processes, at community, family, and individual levels. We will compare our results to those obtained in the U.S. and other countries, to assess the relative impacts of infection, inflammation, lifestyle, and heritability o cardiovascular and metabolic health over the life course.