Exceptional Aging Across the Life Span: Framingham Study

整个生命周期中的异常衰老：弗雷明汉研究

• 批准号: 7615476
• 负责人: JOANNE M MURABITO
• 金额: $ 32万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7615476
• 关键词: Adult; Adult Children; Age; Aging; American; Behavior; Calendar; Cardiovascular system; Child; Chromosomes, Human, Pair 4; Communities; Comorbidity; Data; Databases; Diabetes Mellitus; Disabled Persons; Disease; Elderly; Environment; Environmental Risk Factor; Evaluation; Family Study; Framingham Heart Study; Future; Generations; Genes; Genetic; Genetic Databases; Genetic Determinism; Genome Scan; Genotype; Health; Health Promotion; Heritability; Human; Impaired cognition; Intervention; Knowledge; Lead; Life; Life Cycle Stages; Link; Longevity; Longitudinal Studies; Measures; Morbidity - disease rate; Obesity; Onset of illness; Pathway interactions; Phenotype; Physical activity; Prevalence; Research; Research Personnel; Risk; Risk Factors; Site; Spouses; Time; age related; aging gene; base; cardiovascular risk factor; cognitive function; cohort; disability; disorder prevention; frailty; genetic analysis; genetic variant; genome wide association study; healthy aging; insight; middle age; non-genetic; offspring; prevent; prospective; public health priorities; public health relevance; success; trait; trend

DESCRIPTION (provided by applicant): We propose to comprehensively characterize exceptionally healthy aging and its determinants measured across the adult life span in two generations of community-dwelling adults. Risk factors (RFs) and behaviors associated with common conditions have been found to predict healthy aging. It is not known whether the trajectory of RF changes occurring over the adult life span is associated with a greater impact on healthy aging than RF levels averaged over time or RFs measured in old age. Genetic factors related to longevity and healthy aging remain largely unknown. Given the complexity of human aging, it is likely that many genes contribute to a broad network of basic functions underlying aging. Data from the longitudinal Framingham Heart Study (FHS) original cohort and offspring cohort (adult children of the original cohort and their spouses) can be used to track RF levels over the adult life span, document the occurrence of disease, and relate RF trajectories to aging. The FHS has a comprehensive genetics database that can be used to identify genetic factors related to longevity and healthy aging. We postulate that improvements in exceptionally healthy aging, defined as the absence of comorbidity, physical and cognitive impairment, and frailty, are directly related to decreases in lifetime levels of RFs and behaviors known to predict cardiovascular and other major diseases. We propose to examine the contribution of genetic determinants to longevity and healthy aging traits using heritability and genome-wide association studies (GWAS). The proposal has the following specific aims: Aim 1.To characterizes the prevalence of exceptionally healthy aging among FHS original cohort and offspring cohort who survive to at least age 65 years. Aim 2. To examine whether early and mid-adulthood trajectories of prospectively measured RFs and overall Framingham risk score are better predictors of healthy aging compared to RF levels obtained at old age or RF levels averaged over time. Aim 3. To estimate the genetic contribution to the variance in longevity and healthy aging using a heritability analysis. Aim 4. To identify genetic variants that influence heritable longevity and healthy aging phenotypes through a GWAS using extant genotyping data from a 550k genome scan. Insights from this project may contribute fundamentally to the understanding of the mechanisms responsible for healthy aging and in turn identify directions for health promotion and disease prevention efforts in middle-aged and older adults so that older persons can enjoy more time in good health. PUBLIC HEALTH RELEVANCE: Surveillance of the health of older adults and identification of factors, both genetic and non-genetic, that promote a long and healthy life are important public health priorities. Knowledge gained from this proposal may lead to interventions that prevent age-related disease and disability so that older persons spend more time in good health.

描述（由申请人提供）：我们建议全面地表征异常健康的衰老及其在两代社区居住成年人中均在成人生活中测得的决定因素。发现风险因素（RF）和与常见条件相关的行为可以预测健康的衰老。尚不清楚在成人寿命中发生的RF变化的轨迹对健康衰老的影响是否比随着时间的流逝平均或在老年中测量的RF产生更大的影响。与寿命和健康衰老有关的遗传因素在很大程度上尚不清楚。鉴于人衰老的复杂性，许多基因可能有助于衰老的基本功能的广泛网络。可以使用纵向弗雷明汉心脏研究（FHS）原始队列和后代队列（原始队列及其配偶的成年子女）的数据来跟踪成人寿命中的RF水平，记录疾病的发生，并将RF轨迹与老化有关。 FHS具有一个全面的遗传学数据库，可用于识别与寿命和健康衰老有关的遗传因素。我们假设，改善异常健康的衰老，被定义为缺乏合并症，身体和认知障碍以及脆弱性，与终生的RFS和行为降低直接相关，以预测可以预测心血管和其他主要疾病的行为。我们建议使用遗传力和全基因组关联研究（GWAS）研究遗传决定因素对寿命和健康衰老特征的贡献。该提案具有以下具体目标：目标1.为了表征FHS原始队列和后代同类群体中特殊健康衰老的普遍性，这些衰老生存于至少65岁。目的2。要检查前瞻性测量的RF和整体弗雷明汉风险评分的早期和中期轨迹是否可以更好地预测健康衰老的预测指标，而随着时间的流逝，在老年或RF水平下获得的RF水平是更好的预测指标。目的3。估计使用遗传力分析的遗传贡献对寿命和健康衰老方差的差异。目的4。通过使用550K基因组扫描中现有的基因分型数据来确定通过GWAS通过GWAS影响遗传寿命和健康衰老表型的遗传变异。该项目的见解可能从根本上有助于理解负责健康衰老的机制，进而确定了中年和老年人的健康促进和预防疾病的方向，以便老年人可以享受更多的时间健康。公共卫生相关性：对老年人健康的监视以及促进长期健康生活的遗传和非遗传因素的鉴定是重要的公共卫生优先事项。从该提案中获得的知识可能会导致干预措施，从而预防与年龄相关的疾病和残疾，从而使老年人花费更多的时间健康。