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: 10831367
• 负责人: AVSHALOM CASPI
• 金额: $ 6.66万
• 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/10831367
• 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; Award; Back; Behavioral; Belief; Binding; 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; Dissociation; Elderly; Erectile dysfunction; Ethnic Population; 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; Parents; 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; experience; follow-up; healthspan; high reward; high risk; inflammatory marker; innovation; member; microvascular aging; middle age; mild cognitive impairment; multidisciplinary; novel; participant enrollment; peer; pre-clinical; prevent; programs; prospective; psychosocial; retina blood vessel structure; satisfaction; social; success; vaginal dryness; young adult

PROJECT SUMMARY - NO CHANGES FROM PARENT AWARD 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-与帕萨迪纳奖相比无变化 我们研究项目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。 其他人，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 老年科学家把中年看作是一个提供了一个有利机会来防止或推迟多重性的生命阶段。 使老年人的健康寿命缩短的疾病。但是因为大多数关于衰老的研究都招募了参与者， 大多数对年轻人的研究都没有将衰老作为一个变化的过程来衡量。 然而，令人惊讶的是，关于中年衰老的基本知识很少。我们的研究项目 这个差距。这是一个竞争性的更新建议，在52岁时随访一个出生在一个婴儿出生的所有1037名婴儿的队列。 但尼丁纵向研究（达尼丁纵向研究）。一些群组成员 当他们步入中年时，在生物学上比同龄人更老，其他人在生物学上仍然是 更年轻。拟议的后续行动将使我们能够量化每个队列成员衰老的速度或速度 8个不同领域的每一个：生物老化的速度，功能老化，面部老化，社会老化，性 老化、炎症性老化、微血管老化和认知老化（目标1A）。这8个领域通常是 研究由不同的科学学科在筒仓，但我们将研究他们一起在一个队列，以吸引 科学地认识到整个人对衰老的体验存在巨大的异质性。我们将开发 通过对每种老化的3个或更多波数据进行建模，对8种老化中的每一种进行测量。三个数据波 是解开每个人衰退的最低要求（与衰老有关的衰退，人们如何 改变;他们的斜率）从他们的水平（初始健康，人们开始的地方;他们的截距）。研究较少 超过3个波合并了多年来的下降（老化）和自早期生活以来的低评分（非老化）。的 建议在52岁时进行随访，以便为该参与者队列添加必要的第三次中年波。 这一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，我们将提供 研究社区提供了8种新指标中每一种的可靠，有效，开放获取的DNA甲基化版本。 一个人衰老的速度（目标1B）。评价代表性不足的调查结果的普遍性 种族群体，我们将输出8个新的DNA甲基化措施，以黑人和拉丁裔群体， 甲基化，在那里我们建立了合作研究衰老的速度。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）。我们还将创造新的 了解8种衰老对老年疾病的风险（目标3）。这涉及到测试 假设快速衰老的个体在52岁时表现出健康免疫能力受损 体外反应。它还涉及到测试假设，即快速老化的个人在年龄 52关于阿尔茨海默病的血液生物标志物。

项目成果

DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.

• DOI: 10.1038/s41380-020-00987-x
• 发表时间: 2021-06
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: van Dongen J;Hagenbeek FA;Suderman M;Roetman PJ;Sugden K;Chiocchetti AG;Ismail K;Mulder RH;Hafferty JD;Adams MJ;Walker RM;Morris SW;Lahti J;Küpers LK;Escaramis G;Alemany S;Jan Bonder M;Meijer M;Ip HF;Jansen R;Baselmans BML;Parmar P;Lowry E;Streit F;Sirignano L;Send TS;Frank J;Jylhävä J;Wang Y;Mishra PP;Colins OF;Corcoran DL;Poulton R;Mill J;Hannon E;Arseneault L;Korhonen T;Vuoksimaa E;Felix JF;Bakermans-Kranenburg MJ;Campbell A;Czamara D;Binder E;Corpeleijn E;Gonzalez JR;Grazuleviciene R;Gutzkow KB;Evandt J;Vafeiadi M;Klein M;van der Meer D;Ligthart L;BIOS Consortium;Kluft C;Davies GE;Hakulinen C;Keltikangas-Järvinen L;Franke B;Freitag CM;Konrad K;Hervas A;Fernández-Rivas A;Vetro A;Raitakari O;Lehtimäki T;Vermeiren R;Strandberg T;Räikkönen K;Snieder H;Witt SH;Deuschle M;Pedersen NL;Hägg S;Sunyer J;Franke L;Kaprio J;Ollikainen M;Moffitt TE;Tiemeier H;van IJzendoorn MH;Relton C;Vrijheid M;Sebert S;Jarvelin MR;Caspi A;Evans KL;McIntosh AM;Bartels M;Boomsma DI
• 通讯作者: Boomsma DI

Genetic variants in 5-HTTLPR, BDNF, HTR1A, COMT, and FKBP5 and risk for treated depression after cancer diagnosis.

• DOI: 10.1002/da.22660
• 发表时间: 2017-09
• 期刊: Depression and anxiety
• 影响因子: 7.4
• 作者: Suppli NP;Bukh JD;Moffitt TE;Caspi A;Johansen C;Tjønneland A;Kessing LV;Dalton SO
• 通讯作者: Dalton SO

Group-Based Trajectory Modeling (Nearly) Two Decades Later.

• DOI: 10.1007/s10940-010-9113-7
• 发表时间: 2010-12
• 期刊: JOURNAL OF QUANTITATIVE CRIMINOLOGY
• 影响因子: 3.6
• 作者: Nagin, Daniel S.;Odgers, Candice L.
• 通讯作者: Odgers, Candice L.

Tracing the origins of midlife despair: association of psychopathology during adolescence with a syndrome of despair-related maladies at midlife.

• DOI: 10.1017/s0033291723001320
• 发表时间: 2023-12
• 期刊: PSYCHOLOGICAL MEDICINE
• 影响因子: 6.9
• 作者: Brennan, Grace M.;Moffitt, Terrie E.;Ambler, Antony;Harrington, HonaLee;Hogan, Sean;Houts, Renate M.;Mani, Ramakrishnan;Poulton, Richie;Ramrakha, Sandhya;Caspi, Avshalom
• 通讯作者: Caspi, Avshalom

The Origins of Cognitive Deficits in Victimized Children: Implications for Neuroscientists and Clinicians.

• DOI: 10.1176/appi.ajp.2016.16030333
• 发表时间: 2017-04-01
• 期刊: The American journal of psychiatry
• 作者: Danese A;Moffitt TE;Arseneault L;Bleiberg BA;Dinardo PB;Gandelman SB;Houts R;Ambler A;Fisher HL;Poulton R;Caspi A
• 通讯作者: Caspi A