Understanding Susceptibility to Olfactory Decline in Aging

了解衰老过程中嗅觉下降的易感性

• 批准号: 8449584
• 负责人: JAYANT M PINTO
• 金额: $ 15.4万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8449584
• 关键词: Abbreviations; Affect; Age; Aging; American; Award; Behavior; Chicago; Chromosome Mapping; Clinical; Cognitive; Communities; Comorbidity; Complex; Copy Number Polymorphism; DNA; DNA Resequencing; Data; Data Set; Demography; Development; Diagnosis; Diagnostic; Discrimination; Disease; Economics; Elderly; Environmental Exposure; Epidemiologic Studies; Esthesia; Functional disorder; Future; Genes; Genetic; Genetic Heterogeneity; Genetic Polymorphism; Genetic Variation; Genotype; Gerontology; Goals; Head and Neck Surgery; Health; Home environment; Human; Impaired cognition; Impairment; Individual; Lead; Life; Life Style; Linkage Disequilibrium; Lung diseases; Master' s Degree; Measures; Medical; Medical History; Memory; Mental Depression; Mentorship; Modality; Modeling; Molecular Profiling; Nose; Odds Ratio; Otolaryngology; Participant; Pathogenesis; Performance; Personal Satisfaction; Phenotype; Physical Function; Physiology; Population; Population Study; Predisposing Factor; Predisposition; Probability Samples; Process; Public Health; Quality Control; Quality of life; Quantitative Trait Loci; Religion and Spirituality; Research; Resources; Retirement; Risk; Risk Factors; Safety; Sampling; Scientist; Sensory; Sensory Disorders; Sexuality; Signal Transduction; Single Nucleotide Polymorphism; Smell Perception; Social Conditions; Social Functioning; Socioeconomic Status; Specimen; Stress; Structure; Testing; Therapeutic; Time; Training; Training Programs; Universities; Variant; Work; age related; career; cohort; demographics; density; experience; gene discovery; genetic association; genetic epidemiology; genetic risk factor; genome wide association study; hutterite; improved; insight; interdisciplinary collaboration; meetings; multidisciplinary; non-genetic; novel strategies; nutrition; pleasure; prognostic; programs; psychologic; psychosocial; skills; social; trait

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.

描述（由申请人提供）：与年龄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。这种感觉障碍给老年人的日常生活带来了沉重的负担，与生活质量的大幅下降有关，影响了安全、营养、愉悦感和总体幸福感等关键功能。由于嗅觉会随着时间的推移而减弱，因此随着人口老龄化，临床影响将会增加。先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。 在本申请中，我建议描述与 Ag 相关的嗅觉下降易感性背后的因素。我计划利用记忆与衰老项目 (MAP) 和国家社会生活、健康和老龄化项目 (NSHAP) 的数据来确定与年龄相关的嗅觉衰退相关的生物人口统计学因素。这些强大的资源之前已收集了健康和嗅觉数据以及相关的生物测量数据，将有助于分析与老年人嗅觉丧失相关的医学和心理社会参数。与此同时，我将利用 MAP 和 Hutterites 中的现有基因型数据进行全基因组关联研究 (GWAS)，以检查该表型的遗传风险因素。Hutterites 群体在遗传图谱方面具有许多独特的优势，包括统一的环境暴露和有关相关共病的丰富临床信息。这一系列研究将涉及对几种嗅觉特征的分析，以识别与嗅觉衰退有关的基因。最后，我将使用可用的高质量 DNA 样本，在 NSHAP 中复制这些遗传关联。 结构化培训计划将包括遗传流行病学和人口统计学课程，以培养分析专业知识，最终获得硕士学位。三位在遗传学、人口学和老龄化方面拥有丰富经验的著名科学家将进行多学科指导。该奖项将使我能够培养指导一项关于嗅觉衰退和其他鼻部疾病对老年人影响的独立研究项目所需的技能。 这种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下降的病理生理学，最终可以改善预后、诊断和治疗方式。这些研究的完成将成为理解衰老过程中感觉衰退的非遗传和遗传影响的模型。