Understanding Susceptibility to Olfactory Decline in Aging

描述（由申请人提供）：与年龄相关的嗅觉丧失是影响大约1400万美国老年人的重要公共卫生问题。这种感觉障碍在老年人日常生活中造成的沉重负担与生活质量的大幅下降有关，影响安全、营养、愉悦感和一般福祉等关键功能。因为嗅觉会随着时间的推移而下降，临床影响会随着人口的老龄化而增加。先前对人类嗅觉生理衰退的研究是有限的，需要新的方法来理解影响这一过程的因素。在这个应用程序中，我建议表征的因素，潜在的易感性，以年龄相关的嗅觉下降。利用记忆和衰老项目（MAP）和国家社会生活、健康和老龄化项目（NSHAP）的数据，我计划确定与年龄相关的嗅觉衰退相关的生物统计学因素。在这些强有力的资源中，先前已经收集了健康和嗅觉数据以及相关的生物测量，将允许分析与老年人嗅觉丧失相关的医学和社会心理参数。同时，我将利用MAP和Hutterites的现有基因型数据，通过进行全基因组关联研究（GWAS）来检查这种表型的遗传风险因素。Hutterites是一个在遗传定位方面具有许多明显优势的人群，包括统一的环境暴露和丰富的相关合并症临床信息。这方面的研究将包括分析几种嗅觉特征，以确定与嗅觉衰退有关的基因。最后，利用现有的高质量DNA样本，我将在NSHAP中复制这些遗传关联。一个结构化的培训计划将包括遗传流行病学和人口统计学课程，以发展分析专业知识，最终获得硕士学位。导师将由三位在遗传学、人口学和老龄化方面具有丰富经验的知名科学家组成。这个奖项将使我能够发展必要的技能，指导一个独立的研究项目，研究嗅觉衰退和其他鼻腔疾病对老年人的影响。该方法利用三个无与伦比的互补数据集，将深入了解与年龄相关的嗅觉衰退的病理生理学，最终可以改善预后、诊断和治疗方式。这些研究的完成将为理解非遗传和遗传对衰老过程中感官衰退的影响提供一个模型。

DESCRIPTION (provided by applicant): Age-related olfactory loss is an important public health problem affecting approximately 14 million older Americans. The profound burden this sensory impairment causes in the daily lives of older people is associated with a substantially decreased quality of life, affecting critical functions such as safety, nutrition, sensation of pleasure, and general well-being. Because olfaction declines over time, the clinical impact will increase as our population ages. Previous studies of this decline in olfactory physiology in humans have been limited, requiring novel approaches to understanding factors that affect this process. In this application, I propose to characterize factors that underlie susceptibility to ag-related olfactory decline. Using data from the Memory and Aging Project (MAP) and the National Social Life, Health, and Aging Project (NSHAP), I plan to identify biodemographic factors that are associated with age-related olfactory decline. These robust resources, in which health and olfactory data have been collected previously along with relevant biomeasures, will allow an analysis of medical and psychosocial parameters that are associated with olfactory loss in older persons. In parallel, I will examine genetic risk factors for this phenotype by performing genome-wide association studies (GWAS) using existing genotype data in MAP and in the Hutterites, a population which has a number of distinct advantages for genetic mapping, including uniform environmental exposures and rich clinical information on relevant co-morbidities. This line of study will involve analysis of several olfactory traits for identifying gene(s) involved in the decline of the sense of smell. Lastly, using available, high quality DNA specimens, I will replicate these genetic associations in NSHAP. A structured training program will include courses in genetic epidemiology and demography for the development of analytic expertise, culminating in a Master's degree. Mentorship will be multidisciplinary by three renowned scientists who possess significant experience in genetics, demography, and aging. This award will allow me to develop the skills necessary to direct an independent research program on the impact of olfactory decline and other nasal diseases on older persons. This approach, utilizing three unparalleled and complementary data sets, will provide insight into the pathophysiology of age-related olfactory decline which, ultimately, can lead to improved prognostic, diagnostic and therapeutic modalities. Completion of these studies will serve as a model for understanding the non- genetic and genetic influences on sensory decline in aging.