Understanding Susceptibility to Olfactory Decline in Aging

描述（由申请人提供）：与嗅觉相关的嗅觉丧失是一个重要的公共卫生问题，影响着大约1400万美国老年人。这种感觉障碍在老年人的日常生活中造成的沉重负担与生活质量的大幅下降有关，影响到安全，营养，愉悦感和一般幸福感等关键功能。由于嗅觉随着时间的推移而下降，临床影响将随着我们人口的老龄化而增加。以前对人类嗅觉生理学下降的研究有限，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，我建议的特点因素，潜在的易感性与银相关的嗅觉下降。使用来自记忆和衰老项目（MAP）和国家社会生活，健康和衰老项目（NSHAP）的数据，我计划确定与年龄相关的嗅觉下降相关的生物人口因素。这些强大的资源，其中健康和嗅觉数据已收集沿着与相关的生物测量，将允许分析与老年人嗅觉丧失有关的医疗和心理社会参数。与此同时，我将检查这种表型的遗传风险因素进行全基因组关联研究（GWAS），使用现有的基因型数据在MAP和哈特人，一个人口具有一些明显的优势，遗传图谱，包括统一的环境暴露和丰富的临床信息相关的共病。这项研究将涉及分析几种嗅觉特征，以确定参与嗅觉下降的基因。最后，使用可用的高质量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，人口学和衰老方面拥有丰富经验的知名科学家进行多学科指导。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，研究嗅觉下降和其他鼻部疾病对老年人的影响。 这种方法，利用三个无与伦比的和互补的数据集，将提供深入了解与年龄相关的嗅觉衰退的病理生理学，最终可以导致改善预后，诊断和治疗方式。这些研究的完成将作为一个模型，为了解非遗传和遗传对衰老中感觉衰退的影响。 公共卫生相关性：该提案描述了多种方法来理解为什么嗅觉随着年龄的增长而下降，这是数百万老年人的一个负担问题。通过对三组特征鲜明的老年人进行分析，每组都具有独特的研究优势，平托博士将研究导致衰老嗅觉下降的临床和遗传因素。此外，通过该奖项支持的人口统计学，老年学和遗传学培训，平托博士将在这个竞技场中开发新的科学技能，广泛适用于未来的工作，从而在老年耳鼻喉科取得丰硕的事业。

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. PUBLIC HEALTH RELEVANCE: This proposal describes multiple approaches to understanding why the sense of smell decreases with age, a burdensome problem for millions of older persons. Through analyses in three well-characterized groups of older individuals, each with unique advantages for study, Dr. Pinto will examine both clinical and genetic factors that predispose to olfactory decline in aging. Additionally, with training in demography, gerontology, and genetics supported by this award, Dr. Pinto will develop new scientific skills in this arena with wide applicability to future work, allowing for a productive career in geriatric otolaryngolog.