Environment, Novel Aging Outcomes, and Genetics

描述（由申请人提供） 这个指导研究科学家发展奖的目标是支持首席研究员获得研究知识，技能和经验，进行环境，老年学和遗传流行病学研究。该奖项将促进候选人实现发展成为独立调查员的长期目标的能力。拟议的职业发展计划旨在建立在候选人的环境流行病学与遗传学，衰老流行病学和神经毒理学新的培训先前的研究经验。该项目的科学目标是了解长期环境暴露于铅和空气污染如何影响与年龄相关的病理变化，即心脏功能下降，以及两种在环境健康方面研究相对较少的新结果，年龄相关性白内障和听力损失。此外，该项目旨在确定影响老龄化人口对此类污染物敏感性的因素。这些健康终点是老年人经历的主要慢性健康状况，但污染暴露可能影响这些与年龄有关的疾病的生物学机制却知之甚少。候选人将不仅检查铅和交通相关颗粒的独立影响，而且关注参与铁调节代谢途径的基因，这可能会改变铅和颗粒的反应。研究人员还将检查污染物与年龄相关疾病之间的关联是否会因膳食摄入抗氧化剂（维生素C和E，类胡萝卜素和十字花科蔬菜）和ω-3脂肪酸而改变。为了将候选人过去的研究背景应用于基因-环境相互作用和老龄化流行病学领域的这些研究目标，需要额外的培训和指导。拟议的职业发展计划包括与金属和空气污染流行病学、遗传流行病学、老年流行病学、神经毒理学、眼科学和耳鼻喉科的知名专家合作，并通过教学课程、实验室培训和参加研讨会和国家/国际会议得到加强。本提案将利用来自大型、表型良好、正在进行的社区老年男性纵向队列（规范性老龄化研究）的数据和存档样本，对于某些特定目标，将使用护士健康研究的子样本。相关性：随着人口老龄化的增长，需要更好地了解与年龄相关的病理变化的原因，但对环境污染物对这些与年龄相关的疾病的影响知之甚少。该项目将确定在基因多态性和营养摄入方面哪个亚群体更容易受到铅和空气污染的环境暴露，并最终提出预防性公共卫生战略，以提高老年人口的生活质量。

DESCRIPTION (provided by applicant) The goal of this Mentored Research Scientist Development Award is to support the Principal Investigator to gain the research knowledge, skills and experience to conduct environmental, gerontological and genetic epidemiology studies. This award will promote the candidate's ability to achieve the long-term goal of developing into an independent investigator. The proposed career development plan aims to build on the candidate's prior research experience in environmental epidemiology with new training in genetics, epidemiology of aging, and neurotoxicology. The scientific goals of this project are to understand how long term environmental exposures to lead and air pollution affect age-related pathological changes, namely, depressed cardiac function, and two novel outcomes that have been relatively little studied in environmental health, age-related cataract and hearing loss. In addition, the project aims to identify factors that impact susceptibility to such pollutants in an aging population. These health endpoints are leading chronic health conditions experienced by the older adults, but the biological mechanisms by which pollution exposures may impact these age-related conditions are poorly understood. The candidate will not only examine independent effects of lead and traffic-related particles, but focus on genes involved in the pathway of iron regulation metabolism which may modify the lead and particle responses. The investigator will also examine if the associations between pollutants and age-related diseases are modified by dietary intake of antioxidants (vitamins C and E, carotenoids, and cruciferous vegetables) and omega-3 fatty acids. In order to apply the candidate's past research background in these research aims in the field of gene-environment interaction and epidemiology of aging, additional training and mentorship is necessary. The proposed career development plan includes working with established experts in metals and air pollution epidemiology, genetic epidemiology, gerontological epidemiology, neurotoxicology, ophthalmology and otolaryngology, and is enhanced by didactic coursework, laboratory training and attendance in seminars and national/international meetings. This proposal will take advantage of the data and archived samples from a large, well-phenotyped, on-going, longitudinal cohort of community-residing elderly men, the Normative Aging Study, and for some of the specific aims, a sub-sample of the Nurses' Health Study will be utilized. Relevance: As the aging population grows, the need to better understand the causes of age-related pathological changes is required, but little is known about the impacts of environmental pollutants on such age-related diseases. This project will identify which sub-population in terms of genetic polymorphisms and nutrient intakes is more susceptible to environmental exposures to lead and air pollution, and ultimately suggest preventive public health strategies to improve the quality of life in the aging population.