Midlife Aging in the Dunedin Study Phase 52

但尼丁研究第 52 阶段的中年老龄化

• 批准号: MR/X021149/1
• 负责人: Terrie Moffitt
• 金额: $ 168.37万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX021149%2F1
• 关键词: Midlife; Aging; Dunedin; Study; Phase

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 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, in New Zealand. 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 (Objective 1). 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. We will further generate new knowledge about the early-life antecedents of each kind of aging (Objective 2). We will also generate new knowledge about the risk each of the 8 kinds of aging poses for late-life dementing disease (Objective 3). This involves testing the hypothesis that fast-aging individuals exhibit accelerated brain aging. This will be established through a second wave of neuroimaging at age 52. We previously imaged the brains of Dunedin participants at age 45. We will test 7-year changes in functional neural connectivity and clinical measures of brain structure, while correcting for measurement error. It also involves testing the hypothesis that fast-aging individuals have elevated scores at age 52 on plasma Alzheimers disease biomarkers. 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 (Objective 4). To evaluate generalizability of findings for under-represented ethnic-ancestry groups, we will export the 8 new DNA-methylation measures to Black, Hispanic, and Asian cohorts with methylation, where we have established collaborations to study the pace of aging.

我们的研究计划的首要目标是发现为什么有些人比其他人衰老得更早，更快，以及可以做些什么来防止这种情况。越来越多的具有预防意识的老年病学家和老年科学家将中年视为一个生命阶段，为预防或延迟导致老年人健康寿命缩短的多种疾病提供了有利的机会。但是，由于大多数关于衰老的研究招募的参与者都已经过了中年，而且大多数关于年轻人的研究都没有将衰老作为一个随时间变化的过程来衡量，因此令人惊讶的是，关于中年衰老的基本知识很少。我们的研究计划独特地填补了这一空白。这是一项在新西兰达尼丁纵向研究中，对一个城市在一年内出生的所有1037名婴儿进行52岁随访的建议。一些同龄人在经历中年后，在生理上比同龄人更老，另一些人在生理上仍然更年轻。拟议的随访将使我们能够量化每个队列成员在8个不同领域中老化的速度或速度：生物老化，功能老化，面部老化，社会老化，性老化，炎症老化，微血管老化和认知老化（目标1）。这8个领域通常由不同的科学学科在筒仓中进行研究，但我们将在一个队列中一起研究它们，以吸引科学界对整个人衰老经历中巨大异质性的认识。我们将通过对每种老化的3个或更多波数据进行建模，来开发8种老化中每一种的测量方法。三个数据波是将每个人的衰退（与衰老相关的衰退，人们如何变化;他们的斜率）与他们的水平（初始健康，人们开始的地方;他们的截距）分开的最低要求。少于3个波的研究将多年来的下降（衰老）与早期生活（非衰老）以来的低评分合并。建议在52岁时进行随访，以便为该队列的参与者添加必要的第3个中年波。这一后续行动将创建一个前所未有的独特数据集。我们将进一步产生关于每种衰老的早期前因的新知识（目标2）。我们还将产生关于8种衰老对老年痴呆症的风险的新知识（目标3）。这涉及到测试快速老化的人表现出大脑加速老化的假设。这将通过52岁时的第二波神经成像来确定。我们之前对45岁的达尼丁参与者的大脑进行了成像。我们将测试功能神经连接和大脑结构临床测量的7年变化，同时校正测量误差。它还涉及测试快速老化个体在52岁时血浆阿尔茨海默病生物标志物得分升高的假设。为了扩大科学进步，我们将向研究界提供一个可靠的，有效的，开放获取的DNA甲基化版本的8个新的衡量一个人衰老速度的指标（目标4）。为了评估研究结果对代表性不足的种族祖先群体的普遍性，我们将把8种新的DNA甲基化指标输出到黑人、西班牙裔和亚洲甲基化队列，我们已经在这些队列中建立了研究衰老速度的合作关系。

项目成果

Oral Health-Related Quality of Life from Young Adulthood to Mid-Life.

• DOI: 10.3390/healthcare11040515
• 发表时间: 2023-02-09
• 期刊: HEALTHCARE
• 影响因子: 2.8
• 作者: Hong, Chuen Lin;Thomson, W. Murray;Broadbent, Jonathan M. M.
• 通讯作者: Broadbent, Jonathan M. M.

Educational Mobility, the Pace of Biological Aging, and Lifespan in the Framingham Heart Study

• DOI: 10.1101/2023.11.04.23298091
• 发表时间: 2023-11
• 作者: G. Graf;A. E. Aiello;A. Caspi;M. Kothari;H. Liu;T. Moffitt;P. Muennig;C. Ryan;K. Sugden-K.-S

Kidney-Function Trajectories From Young Adulthood to Midlife: Identifying Risk Strata and Opportunities for Intervention.

• DOI: 10.1016/j.ekir.2022.10.005
• 发表时间: 2023-01
• 期刊: KIDNEY INTERNATIONAL REPORTS
• 影响因子: 6
• 作者: Guiney, Hayley;Walker, Robert;Broadbent, Jonathan;Caspi, Avshalom;Goodin, Elizabeth;Kokaua, Jesse;Moffitt, Terrie E.;Robertson, Stephen;Theodore, Reremoana;Poulton, Richie;Endre, Zoltan
• 通讯作者: Endre, Zoltan

Associations Between Thinner Retinal Neuronal Layers and Suboptimal Brain Structural Integrity in a Middle-Aged Cohort.

• DOI: 10.2147/eb.s402510
• 发表时间: 2023
• 期刊: EYE AND BRAIN
• 影响因子: 4.4
• 作者: Barrett-Young, Ashleigh;Abraham, Wickliffe C.;Cheung, Carol Y.;Gale, Jesse;Hogan, Sean;Ireland, David;Keenan, Ross;Knodt, Annchen R.;Melzer, Tracy R.;Moffitt, Terrie E.;Ramrakha, Sandhya;Tham, Yih Chung;Wilson, Graham A.;Wong, Tien Yin;Hariri, Ahmad R.;Poulton, Richie
• 通讯作者: Poulton, Richie

Test-retest reliability and predictive utility of a macroscale principal functional connectivity gradient.

• DOI: 10.1002/hbm.26517
• 发表时间: 2023-12-15
• 期刊: HUMAN BRAIN MAPPING
• 影响因子: 4.8
• 作者: Knodt, Annchen R.;Elliott, Maxwell L.;Whitman, Ethan T.;Winn, Alex;Addae, Angela;Ireland, David;Poulton, Richie;Ramrakha, Sandhya;Caspi, Avshalom;Moffitt, Terrie E.;Hariri, Ahmad R.
• 通讯作者: Hariri, Ahmad R.