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

项目总结 我们研究计划的首要目标是发现为什么有些人衰老得更早、更快。 其他人，以及可以做些什么来防止这种情况。越来越多具有预防意识的老年学家和 老年学家将中年视为生命阶段，提供了预防或延缓多发性疾病的良机 缩短老年人健康寿命的疾病。但因为大多数关于衰老的研究都招募了参与者 已经过了中年，而且大多数对年轻人的研究都没有将衰老衡量为一个变化的过程 令人惊讶的是，人们对中年衰老的基本知识知之甚少。我们的研究项目独一无二地填补了 这个缺口。这是一项相互竞争的更新建议，目的是在52岁时对所有1037名出生在一个婴儿中的婴儿进行跟踪调查。 一年的城市和从那以后的详尽研究：达尼丁纵向研究。一些队列成员 在进入中年的过程中，他们在生理上比同龄人更老，其他人则在生理上保持不变 更年轻。拟议的后续行动将使我们能够量化每个队列成员在 8个不同领域中的每一个：生物老化、功能老化、面部老化、社会老化、性老化的速度 老化、炎症性老化、微血管老化和认知老化(目标1A)。这8个域通常是 在竖井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 科学地认识到整个人的衰老经历中的巨大异质性。我们将发展 对8种老化类型中的每一种都进行测量，方法是在每种类型上模拟3个或更多的数据波动。三个数据波 解开每个人的衰退的最低要求是什么(衰老相关的衰退，人们如何 改变；他们的斜率)从他们的水平(最初的健康，人们开始的地方；他们的拦截)。更少的研究 超过3次的浪潮将多年的衰退(衰老)与早年以来的低得分(而不是衰老)混为一谈。这个 建议在52岁时进行随访是必要的，以便为这群参与者增加必要的第三次中年浪潮。 这一后续行动将创建史无前例的独特数据集。为了扩大科学进步，我们将向 研究社区提供了可靠、有效、开放获取的DNA甲基化版本，其中每一种都是 一个人衰老的速度(目标1B)。评估代表不足的调查结果的概括性 ，我们将向黑人和拉丁裔人群输出8项新的DNA甲基化措施 甲基化，我们已经建立了合作来研究衰老的速度。我们将进一步产生 关于每种衰老的早期生活先兆的新知识(目标2)。我们还将产生新的 了解8种老龄化对晚年疾病构成的风险(目标3)。这涉及到测试 假设快速老龄化的个体在52岁时表现出建立健康免疫力的能力受损 体外反应。它还涉及到检验一个假设，即快速老龄化的个体在年龄上得分较高。 52关于阿尔茨海默病的血液生物标记物。

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.