Training in Molecular Epidemiology: Linking Genes to Physical Function in Older Adults

分子流行病学培训：将基因与老年人的身体功能联系起来

• 批准号: 9751693
• 负责人: Adam J Santanasto
• 金额: $ 11.65万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751693
• 关键词: Address; Adopted; Aerobic; Aged, 80 and over; Aging; Animals; Area; Award; Bioinformatics; Biological; Biological Assay; Biological Markers; Biological Process; Biology of Aging; Biometry; Blood; Body Weight decreased; Cell Culture Techniques; Cells; Clinical; Cohort Analysis; Consultations; DNA; Data; Elderly; Enzyme-Linked Immunosorbent Assay; Epidemiologic Methods; Epidemiologist; Epidemiology; Equilibrium; Expression Profiling; Family; Family Study; Fibrosis; Foundations; Functional disorder; Funding; Gene Proteins; Genes; Genetic; Genetic Polymorphism; Genetic Transcription; Genomic Segment; Geroscience; Health Care Costs; Healthcare; Heart; Heart failure; Human; Human Genetics; Impairment; Institutionalization; Intervention; Investments; K-Series Research Career Programs; Knowledge; Lead; Life; Life Style; Link; Liver diseases; Longevity; Maps; Measures; Mentors; Mentorship; Messenger RNA; Meta-Analysis; Methods; Mitochondria; Molecular; Molecular Biology; Molecular Epidemiology; Multicenter Studies; Muscle; Myocardial; N-terminal; Natural regeneration; Pathogenicity; Pathway interactions; Phenotype; Physical Function; Physical activity; Plasma; Plasma Proteins; Population; Positioning Attribute; Postdoctoral Fellow; Procollagen; Proteins; Public Health; RNA; Research; Research Personnel; Research Training; Role; Sampling; Serum; Severity of illness; Signal Transduction; Signaling Protein; Skeletal Muscle; TGF Beta Signaling Pathway; Testing; Tissues; Training; Transducers; Transforming Growth Factor beta; United States National Institutes of Health; Walking; age related; age-related muscle loss; base; biomarker development; career; cohort; density; design; disability; epidemiology study; follow-up; functional decline; genetic epidemiology; genetic linkage analysis; genetic variant; genome wide association study; genome-wide; genome-wide linkage; genomic epidemiology; high risk; improved; innovation; insight; intervention effect; lifestyle intervention; mRNA Expression; mortality; muscle aging; novel; potential biomarker; premature; prevent; protein biomarkers; skeletal muscle differentiation; skills; statistics; strength training; therapeutic target

Age-related declines in physical function are common and lead to increased health care costs, institutionalization and mortality. As a traditional epidemiologist with unique expertise in skeletal muscle aging and physical function, I have researched lifestyle interventions (weight loss, aerobic and resistance training) to prevent age-related declines in physical function. However, lifestyle changes are difficult to adopt, especially for those at the highest risk for functional decline. To extend the benefits of these interventions, it is imperative to understand biological processes underlying changes in function with aging and following intervention. As such, the current proposal will provide the candidate with advanced training in molecular epidemiology and biology of aging, yield novel insight on the genetic and biological basis of physical function among older adults and lay the foundation for future research. Specially, Aim 1 will identify genes and genetic variants for physical function and changes in physical function with aging. Aim 2 will examine blood RNA expression for components of the transforming growth factor beta (TGF-β) pathway, which is implicated in muscle dysfunction and pathogenic fibrosis, with physical function and its change with aging. Aim 3 will test if serum levels of TGF-β and procollagen type 3 N- terminal propeptide (P3NP - a biomarker of pathogenic fibrosis) are related physical function among older adults. I will leverage robustly collected physical function measures, biological samples, and an ultra-high-density genome-wide polymorphism map from the NIA-funded Long Life Family Study (LLFS), a multi-center study of exceptional aging and longevity in families and from The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium . The proposed research and training is very innovative. First, despite being implicated in several age-related conditions there have been no human studies that have examined the relationship between TGF-β or P3NP and physical function. Further, LLFS has a large number of “oldest old”, who are understudied and at the highest risk for functional decline. There has also been limited research on the genetics of physical function. The proposed career development award will provide the applicant with essential new mentorship, knowledge and skills in human genetics and molecular epidemiology including but not limited to blood RNA expression and protein biomarker development (Aim 2 and 3), genome wide association (GWA) and linkage analyses (Aim 1 ), meta-analysis (Aim 1) and bioinformatics (Aim 1) approaches to follow-up association and linkage analyses. Finally, this award will be critical for facilitating my transition to an independent research career in aging and molecular epidemiology with a focus on physical function. As an epidemiologist with expertise in both traditional and molecular methods, I will be well-positioned to contribute to the advancement of the evolving field of GeroScience.

与年龄相关的身体机能下降很普遍，并导致医疗保健成本增加，制度化和 死亡。作为传统的流行病学家，在骨骼肌衰老和身体机能方面具有独特的专业知识，我有 研究的生活方式干预措施（减肥，有氧和抵抗训练），以防止与年龄相关的身体下降 功能。但是，生活方式的改变很难采用，尤其是对于那些具有功能下降风险最高的人而言。到 扩展这些干预措施的好处，必须了解功能变化的生物学过程 随着老化和干预。因此，当前的提案将为候选人提供高级培训 分子流行病学和衰老的生物学，对身体机能的遗传和生物学基础产生新的见解 在老年人中，为将来的研究奠定了基础。特别是，AIM 1将确定基因和遗传变异 身体功能和随着衰老的身体功能变化。 AIM 2将检查成分的血液RNA表达 在肌肉功能障碍和致病性纤维化中实现的转化生长因子β（TGF-β）途径 随着身体功能及其随着衰老而变化。 AIM 3将测试TGF-β和Procollagen 3型N-的血清水平是否水平 末端前肽（P3NP-致病性纤维化的生物标志物）是老年人的身体功能。我会 利用强大收集的身体功能测量，生物样品和超高密度的全基因组 来自NIA资助的长寿家庭研究（LLFS）的多态性图，这是一项多中心研究，对特殊衰老和 家庭的寿命 基因组流行病学的心脏和衰老研究的同龄人（电荷） 财团 。拟议的研究和培训非常创新。首先，目的地与几个年龄有关 条件没有人类研究检查TGF-β或P3NP与物理之间的关系 功能。此外，LLFS有大量的“最古老的旧”，他们被理解，功能最高的风险 衰退。关于身体机能遗传学的研究也有限。拟议的职业发展奖 将为申请人提供人类遗传学和分子的必不可少的新精神，知识和技能 流行病学包括但不限于血液RNA表达和蛋白质生物标志物发育（AIM 2和3）， 基因组广泛的关联（GWA）和连锁分析（AIM 1 ），荟萃分析 （AIM 1）和生物信息学（目标1） 后续关联和链接分析的方法。最后，该奖项对于支持我的过渡至关重要 从事衰老和分子流行病学的独立研究职业，重点是身体机能。作为 具有传统和分子方法专业知识的流行病学家， 我会很适合为 Geroscience不断发展的领域的发展。