Midlife Aging in the Dunedin Study Phase 52
Lead Research Organisation:
KING'S COLLEGE LONDON
Department Name: Social Genetic and Dev Psychiatry Centre
Abstract
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.
Technical Summary
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. 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). 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). 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, as assessed by 7-year changes in functional neural connectivity and clinical measures of brain structure from neuroimaging. It also involves testing the hypothesis that fast-aging individuals have elevated scores at age 52 on plasma Alzheimer 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.
Organisations
- KING'S COLLEGE LONDON (Lead Research Organisation)
- University of Oslo (Collaboration)
- Columbia University (Collaboration)
- Max Planck Society (Collaboration)
- University of Virginia (UVa) (Collaboration)
- Broad Institute (Collaboration)
- Singapore Eye Research Institute (Collaboration)
- Duke University (Collaboration)
- University of Pennsylvania (Collaboration)
- University of Otago (Collaboration)
- University of Michigan (Collaboration)
- Rigshospitalet (Collaboration)
- University of Exeter (Collaboration)
Publications
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(2024)
Posttraumatic stress disorder, trauma, and accelerated biological aging among post-9/11 veterans.
in Translational psychiatry
Zhang X
(2024)
Distinct trajectories of lung function from childhood to mid-adulthood.
in Thorax
Synergy For The Influence Of The Month Of Birth In ADHD (SIMBA) Study Group
(2023)
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in The lancet. Psychiatry
Xie JK
(2024)
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in The journals of gerontology. Series B, Psychological sciences and social sciences
Sugden K
(2023)
Cross-National and Cross-Generational Evidence That Educational Attainment May Slow the Pace of Aging in European-Descent Individuals.
in The journals of gerontology. Series B, Psychological sciences and social sciences
Bourassa KJ
(2025)
Accelerated Epigenetic Aging and Prospective Morbidity and Mortality Among U.S. Veterans.
in The journals of gerontology. Series A, Biological sciences and medical sciences
King-Hudson TJ
(2025)
Biomarkers of Oxidative and Mitochondrial Stress Are Associated With Accelerated Pace of Aging at Midlife in a Birth Cohort.
in The journals of gerontology. Series A, Biological sciences and medical sciences
Wertz J
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in The American psychologist
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Are trajectories of social isolation from childhood to mid-adulthood associated with adult depression or suicide outcomes.
in Social psychiatry and psychiatric epidemiology
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Childhood Social Isolation as a Predictor of Retinal Neuronal Thickness in Middle Age: A Lifecourse Birth Cohort Study.
in Psychosomatic medicine
Bourassa KJ
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Which Types of Stress Are Associated With Accelerated Biological Aging? Comparing Perceived Stress, Stressful Life Events, Childhood Adversity, and Posttraumatic Stress Disorder.
in Psychosomatic medicine
Nordmo M
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Cognitive Abilities and Educational Attainment as Antecedents of Mental Disorders: A Total Population Study of Males.
in Psychological science
Slutske WS
(2023)
Disordered gambling in a longitudinal birth cohort: from childhood precursors to adult life outcomes.
in Psychological medicine
Brennan GM
(2023)
Tracing the origins of midlife despair: association of psychopathology during adolescence with a syndrome of despair-related maladies at midlife.
in Psychological medicine
Hanna MR
(2024)
Co-occurrence between mental disorders and physical diseases: a study of nationwide primary-care medical records.
in Psychological medicine
Gjerde LC
(2023)
The p factor of psychopathology and personality in middle childhood: genetic and gestational risk factors.
in Psychological medicine
Whitman ET
(2026)
Replicated evidence for an accelerated rate of whole-body aging in schizophrenia.
in Psychological medicine
Lay-Yee R
(2023)
Social isolation from childhood to mid-adulthood: is there an association with older brain age?
in Psychological medicine
Gjerde LC
(2023)
The p factor of psychopathology and personality in middle childhood: Genetic and gestational risk factors - Corrigendum.
in Psychological medicine
Andersen SH
(2024)
The causal effect of mental health on labor market outcomes: The case of stress-related mental disorders following a human-made disaster.
in Proceedings of the National Academy of Sciences of the United States of America
Bourassa KJ
(2023)
Childhood Adversity and Midlife Health: Shining a Light on the Black Box of Psychosocial Mechanisms.
in Prevention science : the official journal of the Society for Prevention Research
Røysamb E
(2023)
Worldwide Well-Being: Simulated Twins Reveal Genetic and (Hidden) Environmental Influences.
in Perspectives on psychological science : a journal of the Association for Psychological Science
MacDonell N
(2023)
Childhood and Adolescent Television Viewing and Metabolic Syndrome in Mid-Adulthood.
in Pediatrics
Poulton R
(2023)
Fear and anxiety: Lessons learned from the Dunedin longitudinal study.
in Neuroscience and biobehavioral reviews
Whitman ET
(2024)
A blood biomarker of the pace of aging is associated with brain structure: replication across three cohorts.
in Neurobiology of aging
Caspi A
(2024)
A nationwide analysis of 350 million patient encounters reveals a high volume of mental-health conditions in primary care.
in Nature. Mental health
Richmond-Rakerd LS
(2026)
Mental health conditions are associated with increased risk of subsequent self-harm, assault and unintentional injuries in two nations.
in Nature. Mental health
Shen X
(2025)
A methylome-wide association study of major depression with out-of-sample case-control classification and trans-ancestry comparison
in Nature Mental Health
Hill ED
(2025)
Prediction of mental health risk in adolescents.
in Nature medicine
Hill ED
(2025)
Author Correction: Prediction of mental health risk in adolescents.
in Nature medicine
Tham YC
(2025)
Building the world's first truly global medical foundation model.
in Nature medicine
Wertz J
(2023)
Genetic associations with parental investment from conception to wealth inheritance in six cohorts.
in Nature human behaviour
Van Der Laan CM
(2025)
Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes.
in Nature genetics
Whitman ET
(2025)
DunedinPACNI estimates the longitudinal Pace of Aging from a single brain image to track health and disease.
in Nature aging
Richmond-Rakerd LS
(2024)
Associations of hospital-treated infections with subsequent dementia: nationwide 30-year analysis.
in Nature aging
Balachandran A
(2025)
Pace of Aging analysis of healthspan and lifespan in older adults in the US and UK.
in Nature aging
Thomas A
(2023)
Diet, pace of biological aging, and risk of dementia in the Framingham Heart Study.
in medRxiv : the preprint server for health sciences
Guiney H
(2023)
Kidney-Function Trajectories From Young Adulthood to Midlife: Identifying Risk Strata and Opportunities for Intervention.
in Kidney international reports
Poulton R
(2023)
The Dunedin study after half a century: reflections on the past, and course for the future.
in Journal of the Royal Society of New Zealand
Ruiz B
(2025)
Caries Trajectories From Childhood to Adulthood Associated With Mental Disorders in Midlife.
in Journal of public health dentistry
Ruiz B
(2023)
Childhood caries is associated with poor health and a faster pace of aging by midlife.
in Journal of public health dentistry
Bourassa KJ
(2025)
Examining the timing of trauma, PTSD onset, and DNA methylation: A multicohort investigation of candidate CpG sites.
in Journal of psychiatric research
Barnes JC
(2024)
Using risk of crime detection to study change in mechanisms of decision making.
in Journal of personality and social psychology
Sunde HF
(2026)
Parental income and psychiatric disorders from age 10 to 40: a genetically informative population study.
in Journal of child psychology and psychiatry, and allied disciplines
| Title | DunedinPACE an epigenetic measure of the whole-body pace of human biological aging |
| Description | DunedinPACE an epigenetic measure of the whole-body pace of human biological aging |
| Type Of Material | Physiological assessment or outcome measure |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | Imported into 28 large cohort studies, generated >40 publications by other teams |
| Description | Aaron Reuben, iniversity of Virginia Dept of Psychology |
| Organisation | University of Virginia (UVa) |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | ideas, analysis plans, data, analyses, writing, publications |
| Collaborator Contribution | ideas, analysis plans, data, analyses, writing, publications |
| Impact | several publications |
| Start Year | 2023 |
| Description | Columbia Univ School of Public Health |
| Organisation | Columbia University |
| Department | School of Public Health |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | we provide data |
| Collaborator Contribution | Columbia provides funded young researcher |
| Impact | none yet |
| Start Year | 2012 |
| Description | Duke University Geriatrics School of Medicine |
| Organisation | Duke University |
| Department | School of Medicine Duke |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | coauthor papears |
| Collaborator Contribution | coauthor papers |
| Impact | PNAS publication |
| Start Year | 2014 |
| Description | Evan Macosko, Genomics, Broad Institute, MIT. |
| Organisation | Broad Institute |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Shared depletable tissue |
| Collaborator Contribution | New Technology |
| Impact | genomics |
| Start Year | 2021 |
| Description | Go-DMC methylation consortium |
| Organisation | University of Exeter |
| Department | Exeter University Arts Faculty |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | data collaboration |
| Collaborator Contribution | data collaboration |
| Impact | none yet |
| Start Year | 2018 |
| Description | Leah Richmond-Rakerd, Univ of Michigan Dept pf Psychology |
| Organisation | University of Michigan |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Data, writing, analyses, planning projects |
| Collaborator Contribution | Data, writing, analyses, planning projects |
| Impact | several publications and grants |
| Start Year | 2022 |
| Description | MAx Planck Institute of Psychiatry |
| Organisation | Max Planck Society |
| Department | Max Planck Institute of Psychiatry |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | replication on findings in independent studies |
| Collaborator Contribution | replication of findings |
| Impact | publication |
| Start Year | 2010 |
| Description | PROMENTA Centre University of Oslo Norway |
| Organisation | University of Oslo |
| Country | Norway |
| Sector | Academic/University |
| PI Contribution | PROMENTA Centre University of Oslo Norway |
| Collaborator Contribution | collab |
| Impact | Psychology, public health |
| Start Year | 2018 |
| Description | Rijkshospitalet Psychiatry Denmark |
| Organisation | Rigshospitalet |
| Department | Rigshospitalet |
| Country | Denmark |
| Sector | Hospitals |
| PI Contribution | coauthor and train students |
| Collaborator Contribution | data registries |
| Impact | publication |
| Start Year | 2014 |
| Description | Singapore Eye Inst Retinal micro-vasculature |
| Organisation | Singapore Eye Research Institute |
| Country | Singapore |
| Sector | Academic/University |
| PI Contribution | we contributed the cohort sample, and wrote the papers |
| Collaborator Contribution | SERI did the grading of digital retinal photos |
| Impact | 2 papers in press |
| Start Year | 2010 |
| Description | The Dunedin Multidisciplinary Health & Development Study, Otago School of Medicine |
| Organisation | University of Otago |
| Department | Dunedin Multidisciplinary Health & Development Research Unit |
| Country | New Zealand |
| Sector | Academic/University |
| PI Contribution | We raised funds and designed protocols and analysed the data |
| Collaborator Contribution | the Unit at Otago runs the cohort study and undertakes data-collection waves |
| Impact | over 1000 publications |
| Description | Univ of Pennsylvania studies of child abuse |
| Organisation | University of Pennsylvania |
| Department | Department of Psychology |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | we provided data |
| Collaborator Contribution | data and idea exchange |
| Impact | 2 articles |
| Start Year | 2007 |