Midlife Pace of Aging in the Dunedin Study

Lead Research Organisation: King's College London
Department Name: Social Genetic and Dev Psychiatry Centre

Abstract

Declining fertility rates, aging of the baby-boomers, and increasing life expectancy are leading to population aging. As the population ages, this increases the public-health burden of age-related conditions, such as cardiovascular disease, type 2 diabetes, and dementia. Treating un-prevented diseases in late life has proven costly and ineffective. It is now known that potentially preventable risk exposures and physiological causes of age-related disease emerge in childhood. This recognition lends new scientific significance to studies that have followed cohorts from childhood. It is also now known that the pathogenesis of age-related diseases involves gradually accumulating decline in organ systems, beginning in the first half of the life course. Consequently, new interventions aiming to prevent age-related diseases will have to be applied to individuals while they are yet young, before they reach midlife. Translation of basic-science gerontology discoveries into preventive interventions for young humans is lacking because virtually nothing is known about the process of biological aging during the first half of the life course. This prompts our proposal to study the pace of biological aging from the twenties forward. We will use the Dunedin Multidisciplinary Health & Development Study, a longitudinal study of a birth cohort now entering its fifth decade. This study combines methods of demographic/economic surveys, clinical-quality health assessments, biobanking, and linkage to nationwide administrative records (health, welfare, finances). We propose to administer a full-day data-collection protocol to the 1004 living members of the birth cohort. To assess each cohort member's pace of biological aging we will: (a) measure biomarkers across multiple organ systems, and (b) statistically model correlated change in these biomarkers assessed at ages 26, 32, 38, and 45 years. We will describe individual variation in the pace of aging, plus its developmental origins, genomic signatures, functional consequences, associated cognitive changes, and economic costs. We will identify attributes that set apart individuals whose bodies are months or years younger than their chronological age. The proposed work will improve knowledge by generating findings to support future interventions during midlife or earlier, to slow aging, prevent age-related disease, and improve the quality of longer lives.

Technical Summary

Declining fertility rates, aging of the baby-boomers, and increasing life expectancy are leading to population aging. As the population ages, this increases the public-health burden of age-related conditions, such as cardiovascular disease, type 2 diabetes, and dementia. Treating un-prevented diseases in late life has proven costly and ineffective. It is now known that potentially preventable risk exposures and physiological causes of age-related disease emerge in childhood. It is also now known that the pathogenesis of age-related diseases involves gradually accumulating decline in organ systems, beginning in the first half of the life course. Consequently, new interventions aiming to prevent age-related diseases will have to be applied to individuals while they are yet young, before they reach midlife. Translation of basic-science geroscience discoveries into preventive interventions for young humans is lacking because virtually nothing is known about the process of biological aging during the first half of the life course. This prompts our proposal to study the pace of biological aging from the twenties forward. We will use the Dunedin Multidisciplinary Health & Development Study, a longitudinal study of a birth cohort now entering its fifth decade. We propose to administer a full-day data-collection protocol to the 1004 living members of the birth cohort. To assess each cohort member's pace of biological aging we will: (a) measure biomarkers across multiple organ systems, and (b) statistically model correlated change in these biomarkers assessed at ages 26, 32, 38, and 45 years. We will describe individual variation in the pace of aging, plus its developmental origins, genomic signatures, functional consequences, associated cognitive changes, and economic costs. We will identify attributes that set apart individuals whose bodies are months or years younger than their chronological age.

Planned Impact

Please see our "Pathways to Impact" statement for specific plans. Briefly...
The intended non-academic beneficiaries of this research are individuals who experience mental disorder, health-care providers, government, and taxpayers at large. Life expectancy is growing longer and longer. Policy makers and citizens
are concerned that our extra years of life should be healthy, productive, and enjoyable, not extra years of disease and disability. The hope of preventing age-related diseases and of increasing health expectancy requires research to identify candidate risk targets that can be treated successfully, in early life. Thus, our proposed research could potentially increase the political will to deliver preventions and treatments to individuals in midlife, before they develop age-related diseases. Such interventions in turn could reduce the burden of mental illness and age-related disease on the health-care delivery service. Reducing the burden of age-related diseases could in turn reduce costs to
government and taxpayers, and increase national productivity and wellbeing for the UK. Here we refer to the MRC Researchfish website's page entitled Dissemination of Research to Non-Academic Audiences for our MRC
Programme Grant, wherein we report the ways in which our research findings have been communicated to nonacademic users in the past 10 years. Full descriptions are provided for the following activities on the Researchfish site. We expect to engage in very similar dissemination activities in the next 5 years.

WWW.ALTMETRIC.COM records the following evidence of Dunedin Study impact beyond the ivory tower since September 2012: 132 published journal articles have 5,636 total mentions, in 262 unique newspaper-articles by science journalists, 232 blogs, 511 Facebook pages, 216 Wikipedia pages, 37 recommendations in Faculty-1000, and 4,148 twitters from 36 countries on all continents (Downloaded 2 September, 2015). In 2014 we were selected by Altmetric-UK as a demonstration research team at the 99th percentile on impact indicators across the different areas of clinical practice, social media, science media journalistic coverage, and policy documents originating in the UK.

In 2015 a 4-episode documentary film on our research was launched: Predict My Future: What makes us who we really are? http://www.moffittcaspi.com/content/science-us. This film series has been bought for distribution by BBC Asia: Brunei, Cambodia, China, Hong Kong, Indonesia, Laos, Macau, Malaysia, Mongolia, Myanmar, N Korea, Palua, Philippines, Singapore, S Korea, Taiwan, Thailand, & Vietnam. It has also been bought for distribution by Education TV Spain, Discovery Poland, Denmark, Sweden, Norway, and Qantas Airlines onboard entertainment. The documentary has only been marketed since December 2015, US and UK purchasers are expected.

High visibility public lectures by TE Moffitt and A Caspi, and our trainees, such as the 2013 Darwin Lecture at Cambridge, and the 2015 Keynote, International Convention of Psychological Science (ICPS)Amsterdam, both are on the internet.
Training videos disseminated to other research teams
Continuing-education teaching for medical professionals

As a result of these public dissemination activities, and others like them, our research under this programme grant
influences policy, as reported in detail on the MRC Researchfish website, which describes the recent examples below.
US Supreme Court Amicus Briefs
British Academy Policy Report
US National Academy of Sciences Panel on Demand for Drugs
Wrote DSM-V diagnosis for conduct disorder, ADHD and ODD
US National Cancer Institute Report
US Institute of Medicine Report
US National Academy of Sciences 21st Century Skills
Canadian Academy of Health Sciences Expert Panel
National Academy of Sciences, Advisory Committee on Law and Justice
Chair policy seminars at the Nuffield Foundation
Early Intervention Next Steps: A report to Her Majesty's Govt. by G Allen MP

Publications

10 25 50

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Belsky DW (2018) Genetic analysis of social-class mobility in five longitudinal studies. in Proceedings of the National Academy of Sciences of the United States of America

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Caspi A (2018) All for One and One for All: Mental Disorders in One Dimension. in The American journal of psychiatry

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Elliott ML (2018) A Polygenic Score for Higher Educational Attainment is Associated with Larger Brains. in Cerebral cortex (New York, N.Y. : 1991)

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Freedman R (2018) Can a Framework Be Established for the Safe Use of Ketamine? in The American journal of psychiatry

 
Description "Mental Disorders in Norway: A Public Health Perspective". (2018). In Norwegian: <>. Norwegian Institute of Public Health. The title translates to "Mental Health in Norway" and is about well-being and prevalence of mental disorders in Norway, published by The Norwegian Institute of Public Health.
Geographic Reach Europe 
Policy Influence Type Citation in other policy documents
Impact "Mental Disorders in Norway: A Public Health Perspective". (2018). In Norwegian: <>. Norwegian Institute of Public Health. https://urldefense.proofpoint.com/v2/url?u=https-3A__www.fhi.no_globalassets_dokumenterfiler_rapporter_psykisk-2Dhelse_psykisk-5Fhelse-5Fi-5Fnorge2018.pdf&d=DwIFAw&c=imBPVzF25OnBgGmVOlcsiEgHoG1i6YHLR0Sj_gZ4adc&r=b2Fq6lZbKqVrnoF6oCx6ctmn6d7Ax7Th7OrHBLkeHgQ&m=Cebauj8UCrwHU9SNWcWUqWVED5vb4vLcFO9qjYuvBe0&s=HvGGyL_hJFsqdEZVBs-KvzyzLjiAFI4PAzOJ1iVy4UE&e= The title translates to "Mental Health in Norway" and is about well-being and prevalence of mental disorders in Norway, published by The Norwegian Institute of Public Health.
URL https://urldefense.proofpoint.com/v2/url?u=https-3A__www.fhi.no_globalassets_dokumenterfiler_rapport...
 
Description Nuffield Council on bioethics Briefing note: the search for a treatment for ageing
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
Impact Nuffield Council on Bioethics, Briefing note: The search for a treatment for ageing. Cites 5 of our publications. (2018)
 
Description ESRC
Amount £200 (GBP)
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 10/2014 
End 09/2017
 
Description NIA Dunedin Phase 45 grant
Amount $3,000,000 (USD)
Funding ID 1R01AG049789-01 
Organisation National Institute on Aging 
Sector Public
Country United States
Start 09/2015 
End 08/2020
 
Description NIA Neuroimaging grant
Amount $7,000,000 (USD)
Funding ID 2 R01 AG032282-06 
Organisation National Institute on Aging 
Sector Public
Country United States
Start 07/2015 
End 06/2020
 
Description Anita Thapar ADHD trajectory project 
Organisation Cardiff University
Department Cardiff Synthetic Biology Initiative
Country United Kingdom 
Sector Academic/University 
PI Contribution data collaboration
Collaborator Contribution data collaboration
Impact not yet
Start Year 2018
 
Description Cambridge Cognition CANTAB 
Organisation Cambridge Cognition Ltd
Country United Kingdom 
Sector Private 
PI Contribution collected data with E-risk twins
Collaborator Contribution measurement technology
Impact n/a
Start Year 2011
 
Description Cardiff Univ replicating genetic findings 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution replication of genetic findings across cohorts
Collaborator Contribution replication of genetic findings across cohorts
Impact Caspi, Thapar, et al. 2008
Start Year 2006
 
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 Data sharing from the Dunedin Study 
Organisation University of Otago
Country New Zealand 
Sector Academic/University 
PI Contribution we collect and share the data
Collaborator Contribution The Dunedin Study data set is shared among a consortium of 6 research teams, from Canada, Australia, New Zealand, and us, in the UK. Via our Unit based at the Univ of Otago in New Zealand, we share the data with more than 80 other research teams outside the Study group, including with 23 universities in the USA. This study has been ongoing since 1972, has a 32 year dataset, and has had 12 assessments.
Impact more than 1200 scientific publications since 1973
 
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 Duke university co-directing phase 18 
Organisation Duke University
Department Insitute of Genome Sciences and Policy
Country United States 
Sector Academic/University 
PI Contribution Moffitt and Caspi have joint appointments at Duke, and are co-investigators in phase 18 of the E-risk study led by Louise Arseneault
Collaborator Contribution ideas
Impact Phase 18 data collection
 
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 Singapore Eye Inst Retinal micro-vasculature 
Organisation Singapore Eye Research Institute
Country Singapore 
Sector Public 
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 SuPAR project 
Organisation University of Copenhagen
Department Center for Healthy Aging
Country Denmark 
Sector Academic/University 
PI Contribution data collaboration
Collaborator Contribution assays collaboration
Impact 2 publications
Start Year 2018
 
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 UCL psychology stuides of callous unemotional traits 
Organisation University College London
Department Division of Psychology & Language Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution we co wrote papers with dr viding
Collaborator Contribution idea and data exchange
Impact 3 publications
Start Year 2007
 
Description Univ of Calif at Irvine Neighbourhood REsearch 
Organisation University of California, Irvine
Country United States 
Sector Academic/University 
PI Contribution E-risk data sharing with team at UC Irvine who has geocoded indicators of neighbourhood level health and poverty indicators to study hwo these affect children's mental health development.
Collaborator Contribution augmented data base
Impact 6 papers in the analysis stage
Start Year 2008
 
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
 
Description University of Otago replications of genetic findings 
Organisation University of Otago
Department Dunedin School of Medicine
Country New Zealand 
Sector Academic/University 
PI Contribution WE replicated findings from the NZ Dunedin cohort in the UK E-risk cohort.
Collaborator Contribution sister studies in two countries, both funded in part by MRC, we can build in replication checks for any and all findings
Impact 4 articles, reported to MRC eval under our other grant, for the Dunedin Study. All are multidisciplinary, involving genetics and pscyhiatry and psychology.
Start Year 2006
 
Description University of São Paulo Medical School and the National Institute of Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil. 
Organisation National Institute of Developmental Psychiatry for Children and Adolescents (INCT-CNPq)
Country Brazil 
Sector Public 
PI Contribution shared data, replicated findings
Collaborator Contribution ideas, publicationsideas, publications
Impact publications
Start Year 2007
 
Description University of São Paulo Medical School and the National Institute of Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil. 
Organisation University of Sao Paulo
Country Brazil 
Sector Academic/University 
PI Contribution shared data, replicated findings
Collaborator Contribution ideas, publicationsideas, publications
Impact publications
Start Year 2007
 
Description methylation and gene expression 
Organisation Free University of Amsterdam
Department Department of Chemistry and Pharmaceutical Sciences
Country Netherlands 
Sector Academic/University 
PI Contribution data collaboration
Collaborator Contribution multi-study
Impact 3 publications
Start Year 2018
 
Description 3-page story about our research in the journal: Science. 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact 3-page feature article about our careers in the Dunedin Study.
Year(s) Of Engagement Activity 2018
URL http://science.sciencemag.org/content/359/6375/510.full
 
Description Human Nature Observed, Science Magazine article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Feature article about our work: commissioned by Science magazine.
Starr, Douglas, Human nature, observed: For decades, two psychologists have kept watch over 1000 New Zealanders, teasing out factors that shape a life's course. Science 02 Feb 2018: Vol. 359, Issue 6375, pp. 510-513. DOI: 10.1126/science.359.6375.510

http://science.sciencemag.org/content/359/6375/510.full
Year(s) Of Engagement Activity 2018
URL http://science.sciencemag.org/content/359/6375/510.full