Aging in 1000 healthy midlife adults: Phase 52 of the Dunedin Study

1000 名健康中年成年人的衰老：但尼丁研究的第 52 阶段

• 批准号: 10516825
• 负责人: AVSHALOM CASPI
• 金额: $ 90.17万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10516825
• 关键词: Adolescence; Adolescent; Adult; Age; Aging; Algorithms; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Animals; Anxiety; Arousal; Asthma; Back; Behavioral; Belief; Biological; Biological Aging; Biological Markers; Birth; Black race; Blood; Blood Tests; Caliber; Cardiovascular Physiology; Childhood; Cities; Cognitive aging; Collaborations; Communities; DNA Methylation; Data; Data Set; Dementia; Dental; Development; Diagnosis; Discipline; Disease; Elderly; Enrollment; Erectile dysfunction; Ethnic group; Face; Fetal Growth; Frequencies; Funding; Gait speed; Goals; Hand Strength; Health; Health Status; Heterogeneity; Image; Immune; Immune response; In Vitro; Individual; Individual Differences; Infant; Inflammatory; Intercept; Interleukin-6; Kidney; Knowledge; Latinx; Life; Life Cycle Stages; Loneliness; Longitudinal Studies; Lung; Measures; Menopause; Mental disorders; Metabolic; Methods; Methylation; Mind; Modeling; Names; Obesity; Ophthalmoscopy; Outcome; Pain; Participant; Persons; Phase; Prevention; Process; Puberty; Publishing; Reporting; Research; Risk; Sexually Transmitted Diseases; Smoking; Social isolation; Social support; System; Testing; Time; Trail Making Test; Urinary Incontinence; Verbal Learning; Walking; Work; balance testing; childhood adversity; cohort; critical period; deprivation; ethnic diversity; exhaustion; experience; follow-up; healthspan; high reward; high risk; inflammatory marker; innovation; member; microvascular aging; middle age; mild cognitive impairment; multidisciplinary; novel; peer; pre-clinical; prevent; programs; prospective; psychosocial; retina blood vessel structure; satisfaction; social; success; vaginal dryness; young adult

PROJECT SUMMARY The overarching goal of our research program is to discover why some people age earlier and faster than others, and what might be done to prevent this. Increasingly, prevention-minded gerontologists and geroscientists look to midlife as the life stage offering a propitious opportunity to prevent or delay the multiple diseases that shrink older adults’ health span. But because most studies of aging have enrolled participants well past midlife, and most studies of younger adults have not measured aging as a process of change over time, there is surprisingly little basic knowledge about aging during midlife. Our research program uniquely fills this gap. This is a competing renewal proposal to follow up at age 52 a cohort of all 1037 infants born in one city in one year and exhaustively studied ever since: the Dunedin Longitudinal Study. Some cohort members are becoming biologically older than their peers as they pass through midlife, others remain biologically younger. The proposed follow-up will allow us to quantify how fast or slowly each cohort member is aging in each of 8 different domains: the pace of biological aging, functional aging, facial aging, social aging, sexual aging, inflammatory aging, microvascular aging, and cognitive aging (Aim 1A). These 8 domains are typically studied by different scientific disciplines in silos, but we will study them together in one cohort to attract scientific recognition to the great heterogeneity within the whole-person experience of aging. We will develop a measure of each of the 8 kinds of aging, by modelling 3 or more waves of data on each. Three data waves are the minimum requirement to disentangle each person’s decline (aging-related decline, how people have changed; their slope) from their level (initial health, where people started; their intercept). Studies with fewer than 3 waves conflate decline over the years (aging) with low scores present since earlier life (not aging). The proposed follow-up at age 52 is necessary to add the essential 3rd midlife wave for this cohort of participants. This follow-up will create an unprecedented unique dataset. To amplify scientific progress, we will deliver to the research community a reliable, valid, open-access DNA-methylation version of each of the 8 new measures of how rapidly a person has been aging (Aim 1B). To evaluate generalizability of findings for under-represented ethnic-groups, we will export the 8 new DNA-methylation measures to Black and Latinx cohorts with methylation, where we have established collaborations to study the pace of aging. We will further generate new knowledge about the early-life antecedents of each kind of aging (Aim 2). We will also generate new knowledge about the risk each of the 8 kinds of aging poses for late-life disease (Aim 3). This involves testing the hypothesis that fast-aging individuals show compromised capacity at age 52 to mount a healthy immune response in vitro. It also involves testing the hypothesis that fast-aging individuals have elevated scores at age 52 on blood biomarkers for Alzheimers disease.

项目摘要 我们的研究计划的总体目标是发现为什么某些人比 其他人，以及可以采取的措施来防止这种情况。越来越多的预防性的老年医学家和 Geroscientist将中年视为生活阶段提供一个有利的机会来预防或延迟倍数 缩小老年人健康范围的疾病。但是因为大多数衰老研究都招募了参与者 过去的中年，大多数对年轻人的研究都没有衡量衰老作为改变的过程 时间，关于中年衰老的基本知识令人惊讶。我们的研究计划独特地填写 这个差距。这是一项相互竞争的续签建议，可在52岁时跟进所有1037名婴儿的队列 一年之内的城市，从那以后进行了详尽的研究：但尼丁纵向研究。一些队列成员 随着中年的过时，他们比同龄人更年长，其他人仍然在生物学上 年轻。提出的随访将使我们能够量化每个队列成员在老化的速度或缓慢的速度 八个不同领域中的每个：生物衰老，功能衰老，面部衰老，社会衰老，性的速度 衰老，炎症老化，微血管衰老和认知衰老（AIM 1A）。这8个域通常是 在孤岛中由不同的科学学科研究，但我们将在一个队列中一起研究它们以吸引 对整个衰老体验中的巨大异质性的科学认识。我们将发展 通过对每种数据的3个或更多数据浪进行建模，对8种衰老中的每种量度进行了衡量。三个数据波 是消除每个人衰落的最低要求（与衰老有关的下降，人们如何 变化；他们的坡度）从他们的水平（最初的健康，人们开始的地方；拦截）。研究更少 多年来，比3波的下降（老龄化）与自早期寿命（不是老化）以来的分数低。这 拟议在52岁时提出的随访对于为参与者群体添加必需的第三次中年浪潮。 此后续行动将创建一个前所未有的独特数据集。为了扩大科学进步，我们将交付给 研究社区是8个新措施的可靠，有效，开放式DNA-甲基化版本 一个人衰老的速度速度（AIM 1B）。评估发现不足的发现的普遍性 族裔群体，我们将与黑人和拉丁人同类的8种新的DNA-甲基化措施一起出口 甲基化，我们已经建立了合作来研究衰老的步伐。我们将进一步生成 关于每种衰老的早期先生的新知识（AIM 2）。我们还将生成新的 关于8种衰老中每种衰老中每种风险的知识（AIM 3）。这涉及测试 迅速衰老的个体在52岁时表现出可损害的能力以实现健康免疫的假设 体外反应。它还涉及检验以下假设：快老人在年龄时的得分升高 52关于阿尔茨海默氏病的血液生物标志物。