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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

基本信息

批准号：
8068869
负责人：
JOANNE M MURABITO
金额：
$ 32.79万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8068869
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 Function 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 success trait trend

项目摘要

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）：我们建议全面描述异常健康的老龄化及其在两代社区居住成年人的整个成年寿命中测量的决定因素。已发现与常见病症相关的风险因素 (RF) 和行为可以预测健康老龄化。目前尚不清楚成人寿命期间发生的射频变化轨迹是否比随时间变化的平均射频水平或老年时测量的射频对健康衰老的影响更大。与长寿和健康衰老相关的遗传因素在很大程度上仍然未知。鉴于人类衰老的复杂性，许多基因可能对衰老背后的广泛基本功能网络做出了贡献。来自纵向弗雷明汉心脏研究 (FHS) 原始队列和后代队列（原始队列的成年子女及其配偶）的数据可用于跟踪成人寿命期间的 RF 水平、记录疾病的发生并将 RF 轨迹与衰老联系起来。 FHS 拥有全面的遗传学数据库，可用于识别与长寿和健康老龄化相关的遗传因素。我们假设，异常健康的老龄化（定义为不存在合并症、身体和认知障碍以及虚弱）的改善与已知可预测心血管和其他主要疾病的 RF 和行为的终生水平降低直接相关。我们建议利用遗传性和全基因组关联研究（GWAS）来研究遗传决定因素对长寿和健康衰老特征的贡献。该提案有以下具体目标：目标 1. 描述 FHS 原始队列和存活至至少 65 岁的后代队列中异常健康老龄化的患病率。目标 2. 与老年时获得的 RF 水平或随时间推移平均的 RF 水平相比，研究前瞻性测量的 RF 和总体弗雷明汉风险评分的成年早期和中期轨迹是否是健康老龄化的更好预测指标。目标 3. 使用遗传力分析来估计遗传对长寿和健康衰老差异的贡献。目标 4. 使用 55 万基因组扫描的现有基因分型数据，通过 GWAS 识别影响可遗传寿命和健康衰老表型的遗传变异。该项目的见解可能会从根本上有助于理解健康老龄化的机制，进而确定中老年人健康促进和疾病预防工作的方向，使老年人能够享受更多的健康时光。公共卫生相关性：监测老年人的健康状况并确定促进长寿和健康生活的遗传和非遗传因素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预防与年龄相关的疾病和残疾的干预措施，从而使老年人有更多的时间保持健康。