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: 8301295
• 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/8301295
• 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. 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.

描述（由申请人提供）：与年龄相关的嗅觉损失是影响约1400万美国人的重要公共卫生问题。这种感官障碍在老年人的日常生活中造成的巨大负担与生活质量大大降低有关，影响了关键功能，例如安全，营养，愉悦感和一般福祉。由于嗅觉随着时间的流逝而下降，随着我们人口年龄的增长，临床影响将增加。先前关于人类嗅觉生理学下降的研究受到限制，需要新颖的方法来理解影响这一过程的因素。 在此应用中，我建议表征对与Ag相关的嗅觉下降敏感的因素。我计划使用内存和老化项目（MAP）以及国家社会生活，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统计学因素。这些坚固的资源，其中以前已经收集了健康和嗅觉数据以及相关的生物衡量，将允许对与老年人嗅觉损失相关的医学和社会心理参数进行分析。同时，我将使用MAP和Hutterites中的现有基因型数据进行全基因组关联研究（GWAS）来检查该表型的遗传危险因素，该人群对遗传学映射具有许多不同的优势，包括统一的环境暴露量和有关相关共同生产率的丰富临床信息。这一研究将涉及分析几种嗅觉性状，以识别与嗅觉下降有关的基因。最后，使用可用的高质量DNA标本，我将在NSHAP中复制这些遗传关联。 一项结构化培训计划将包括遗传流行病学和人口统计学课程，以开发分析专业知识，并在硕士学位上达到顶点。指导将由三位著名科学家进行多学科，他们在遗传学，人口统计学和衰老方面拥有丰富的经验。该奖项将使我能够发展有关嗅觉下降和其他鼻部疾病对老年人的影响的独立研究计划所需的技能。 这种方法利用三个无与伦比和互补的数据集，将提供对与年龄相关的嗅觉下降的病理生理学的见解，最终可以改善预后，诊断和治疗方式。这些研究的完成将是理解非遗传和遗传影响对衰老感觉下降的模型。 公共卫生相关性：该提案描述了多种方法，以理解为什么气味随着年龄的增长而降低，这是数百万老年人的繁重问题。通过对三个特征良好的老年人的分析，每个人都具有独特的研究优势，Pinto博士将检查临床和遗传因素，这些因素和遗传因素易受衰老的嗅觉下降。此外，通过该奖项支持的人口统计学，老年病和遗传学的培训，Pinto博士将在该领域发展具有广泛适用性的新科学技能，从而使老年耳鼻喉科的富有成效的职业。