Generating new knowledge to support reversibility interventions

生成新知识以支持可逆性干预措施

• 批准号: 8799054
• 负责人: TERRIE E MOFFITT
• 金额: $ 15.7万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8799054
• 关键词: Adult; Adverse event; Age; Aging; Behavioral; Biological Aging; Biological Markers; Birth; Cardiovascular Diseases; Child Abuse and Neglect; Childhood; Clinic; Clinical; Cohort Studies; Data; Data Analyses; Data Set; Dementia; Development; Disease; Disease model; Economics; Elderly; Family; Family history of; Funding; Future; General Population; Generations; Genetic; Genetic Risk; Genotype; Half-Life; Health; Individual; Individual Differences; Intervention; Knowledge; Life; Life Cycle Stages; Life Expectancy; Light; Measurement; Measures; Mediating; Mediation; Methods; Modeling; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Outcome Measure; Participant; Pathogenesis; Performance; Policy Maker; Population; Process; Public Health; Publishing; Randomized Clinical Trials; Recommendation; Recording of previous events; Reporting; Research; Research Design; Resources; Risk; Risk Factors; Social Environment; Social isolation; Socioeconomic Status; Specific qualifier value; Speed; Staging; Surveys; Testing; Variant; Work; age related; aging population; body system; cohort; design; disability; evidence base; experience; genome-wide; human subject; improved; interest; middle age; mortality; multidisciplinary; novel; prevent; prospective; psychologic; public health relevance; social

 DESCRIPTION (provided by applicant): This application responds to a call for research on the "mid-life reversibility of early-established bio-behavioral risk factors" (RFA-AG-14-006). Population aging increases the public-health burden of age-related conditions, such as cardiovascular disease, type 2 diabetes, and dementia. It is now known that the pathogenesis of such age- related diseases involves gradually accumulating damage to organ systems, beginning in the first half of the life course, particularly in people exposed to early-life adversty. It is also known that age-related diseases and early mortality are portended by a variety of adverse experiences in early life. Although these facts imply that it is desirable to prevent early life adversities, adversity cannot be fully prevented (and it is too late to prevent early- life adversity for the baby-boomer generation). Therefore there is growing interest in interventions for midlife adults, to reverse the damage done by early-life adversity. This interest lends new scientific significance to existing studies that have followed cohorts from childhood to midlife, because they can provide an evidence base to inform and speed the development of novel intervention strategies. The RFA extends a call for such studies. We propose to undertake data analyses in one such study, the NIA-funded Dunedin Multidisciplinary Health & Development Study, a longitudinal birth-cohort study of both problematic and positive processes of lifelong development. Our data resource comprises in-clinic assessments at birth and ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, and most recently 38 years, with 95% retention as the cohort enters midlife. The data combine demographic/economic surveys, clinical-quality health assessments, a bio-bank, genome-wide SNP data, and administrative-record linkage. First, we will generate outcome measures to detect individual differences in decline of biomarkers for organ systems in the general population at early midlife, the stage when future reversibility interventions will be applied. Second, we will compare the performance of retrospective versus prospective measures of early-life adversity. Future reversibility interventions will have to rely on midlife participants' retrospective reports of adversity, so there is a need to know how well this is going to work. Third, we will test how the connection between early-life adversity and midlife aging relates to polygenic genetic risk and family history of age-related diseases. Will genotype or family history influence responsiveness to reversibility interventions? Fourth, we will identify potentially reversible behavioral and social factors that mediate the connection from early-life adversity to midlife biological aging. Findings are expected to support the design of future randomized clinical trials of midlife interventions intended to reverse the effects of early-life adversity, prevent age-related diseases, and enhance wellbeing in late life.

 描述（由应用程序提供）：本申请响应有关“早期生物行为危险因素的中期可逆性”的呼吁（RFA-AG-14-006）。人口衰老会增加与年龄相关状况的公共卫生燃烧，例如心血管疾病，2型糖尿病和痴呆症。现在众所周知，这种与年龄有关的疾病的发病机理涉及逐渐积累对器官系统的损害，从生命过程的上半年开始，尤其是在暴露于早期寿命的患者中。还众所周知，与年龄相关的疾病和早期死亡率在早期的各种不良经历中所延续。尽管这些事实意味着希望尽早防止 生命逆境，逆境不能完全预防（为时已晚，预防婴儿潮一代的早期逆境为时已晚）。对中年成年人的干预措施越来越兴趣，以扭转早期逆境造成的损害。这种兴趣为从童年到中年的人群遵循的现有研究提供了新的科学意义，因为它们可以提供证据基础，以告知和加快新颖干预策略的发展。 RFA扩展了此类研究的呼吁。我们建议在一项此类研究中进行数据分析，即NIA资助的Dunedin多学科健康与发展研究，这是对终身发展的问题和积极过程的纵向出生研究。我们的数据资源包括出生时和3、5、7、9、11、13、15、18、21、26、32和最近38年的临界评估，随着同伙进入中年，保留了95％。数据结合了人口/经济调查，临床质量的健康评估，生物银行，全基因组SNP数据和行政记录联系。首先，我们将制定成果指标，以检测中年早期人群中器官系统生物标志物下降的个体差异，该阶段将采用将来的可逆性干预措施。其次，我们将比较回顾性的表现与早期广告的前瞻性衡量标准。未来的可逆性干预措施将不得不依靠中年参与者的广告回顾性报告，因此有必要知道这情况如何 上班。第三，我们将测试早期广告与中年衰老之间的联系如何与多基因遗传风险和与年龄相关疾病的家族史有关。基因型或家族史会影响对可逆性干预的响应能力吗？第四，我们将确定潜在的可逆行为和社会因素，这些因素和社会因素介导了从早年广告到中年生物学老化的联系。预计发现将支持未来的中年干预措施的随机临床试验的设计，旨在扭转早期逆境的影响，预防与年龄相关的疾病并增强后期的健康状况。