Publications
Aging
DunedinPACNI estimates the longitudinal Pace of Aging from a single brain image to track health and disease | 2025
Ethan T. Whitman, Maxwell L. Elliott, Annchen R. Knodt, Wickliffe C. Abraham, Tim J. Anderson,
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Nature Aging, 2025, .
https://doi.org/10.1038/s43587-025-00897-z
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Our ref: RO825
To understand how aging affects functional decline and increases disease risk, it is necessary to develop measures of how fast a person is aging. Using data from the Dunedin Study, we introduce an accurate and reliable measure for the rate of longitudinal aging derived from cross-sectional brain magnetic resonance imaging, that is, the Dunedin Pace of Aging Calculated from NeuroImaging (DunedinPACNI). Exporting this measure to the Alzheimer’s Disease Neuroimaging Initiative, UK Biobank and BrainLat datasets revealed that faster DunedinPACNI predicted cognitive impairment, accelerated brain atrophy and conversion to diagnosed dementia. Faster DunedinPACNI also predicted physical frailty, poor health, future chronic diseases and mortality in older adults. When compared to brain age gap, DunedinPACNI was similarly or more strongly related to clinical outcomes. DunedinPACNI is a next-generation brain magnetic resonance imaging biomarker that can help researchers explore aging effects on health outcomes and evaluate the effectiveness of antiaging strategies.
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Biomarkers of oxidative and mitochondrial stress are associated with accelerated pace of aging at midlife in a birth cohort | 2025
King-Hudson, Te-Rina J Pearson, Andree G Dunstan-Harrison, Caitlin Powell, Mathew T Magon,
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The Journals of Gerontology: Series A, 2025, .
10.1093/gerona/glaf105
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Our ref: RO823
Oxidative stress and mitochondrial dysfunction are proposed to play prominent roles in the biology of aging. Human studies are limited and confounded by metabolic disturbances associated with age-related diseases. In this study we have measured biomarkers of oxidative and mitochondrial stress in blood samples from up to 864 participants in the longitudinal Dunedin Multidisciplinary Health and Development Study at age 45. We then determined the correlation between these cross-sectional biomarkers and the longitudinal Pace of Aging, a composite score that represents whole-organism functional decline in each participant from 26 to 45 years old, and facial age at 45 years old. Protein carbonyls and allantoin were selected as biomarkers for oxidative stress, and GDF-15 as a marker of mitochondrial stress. Mid-life levels of these biomarkers were low but varied across the population. GDF-15 showed the strongest associations with the Pace of Aging (β = 0.26, p < 0.0001) and facial age (β = 0.12, p =0.001) in sex and smoking adjusted models. The Pace of Aging was also significantly associated with allantoin (β = 0.14, p < 0.0001) and protein carbonyls (β = 0.09, p = 0.005), and allantoin was also associated with facial age (β = 0.08, p = 0.02). These associations remained when the limited number of participants with age-related disease were removed from the analyses. Our results provide evidence of increased oxidative stress and mitochondrial stress in faster aging humans at midlife, well before the onset of age-related disease.
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A blood biomarker of the pace of aging is associated with brain structure: replication across three cohorts | 2024
Whitman, E. T.; Ryan, C. P.; Abraham, W. C.; Addae, A.; Corcoran,
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Neurobiology of Aging, 2024, 136 23-33.
10.1016/j.neurobiolaging.2024.01.008
Our ref: RO820
Biological aging is the correlated decline of multi-organ system integrity central to the etiology of many age-related diseases. A novel epigenetic measure of biological aging, DunedinPACE, is associated with cognitive dysfunction, incident dementia, and mortality. Here, we tested for associations between DunedinPACE and structural MRI phenotypes in three datasets spanning midlife to advanced age: the Dunedin Study (age=45 years), the Framingham Heart Study Offspring Cohort (mean age=63 years), and the Alzheimer's Disease Neuroimaging Initiative (mean age=75 years). We also tested four additional epigenetic measures of aging: the Horvath clock, the Hannum clock, PhenoAge, and GrimAge. Across all datasets (total N observations=3380; total N individuals=2322), faster DunedinPACE was associated with lower total brain volume, lower hippocampal volume, greater burden of white matter microlesions, and thinner cortex. Across all measures, DunedinPACE and GrimAge had the strongest and most consistent associations with brain phenotypes. Our findings suggest that single timepoint measures of multi-organ decline such as DunedinPACE could be useful for gauging nervous system health.
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Cross-National and Cross-Generational Evidence That Educational Attainment May Slow the Pace of Aging in European-Descent Individuals | 2023
Sugden, K.; Moffitt, T. E.; Arpawong, T. E.; Arseneault, L.; Belsky,
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The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences, 2023, 78(8), 1375-1385.
10.1093/geronb/gbad056
Our ref: RO817
OBJECTIVES: Individuals with more education are at lower risk of developing multiple, different age-related diseases than their less-educated peers. A reason for this might be that individuals with more education age slower. There are 2 complications in testing this hypothesis. First, there exists no definitive measure of biological aging. Second, shared genetic factors contribute toward both lower educational attainment and the development of age-related diseases. Here, we tested whether the protective effect of educational attainment was associated with the pace of aging after accounting for genetic factors. METHODS: We examined data from 5 studies together totaling almost 17,000 individuals with European ancestry born in different countries during different historical periods, ranging in age from 16 to 98 years old. To assess the pace of aging, we used DunedinPACE, a DNA methylation algorithm that reflects an individual's rate of aging and predicts age-related decline and Alzheimer's disease and related disorders. To assess genetic factors related to education, we created a polygenic score based on the results of a genome-wide association study of educational attainment. RESULTS: Across the 5 studies, and across the life span, higher educational attainment was associated with a slower pace of aging even after accounting for genetic factors (meta-analysis effect size = -0.20; 95% confidence interval [CI]: -0.30 to -0.10; p = .006). Further, this effect persisted after taking into account tobacco smoking (meta-analysis effect size = -0.13; 95% CI: -0.21 to -0.05; p = .01). DISCUSSION: These results indicate that higher levels of education have positive effects on the pace of aging, and that the benefits can be realized irrespective of individuals' genetics.
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Childhood caries is associated with poor health and a faster pace of aging by midlife | 2023
Ruiz, B.; Broadbent, J. M.; Thomson, W. M.; Ramrakha, S.; Moffitt,
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Journal of Public Health and Dentistry, 2023, 83(4), 381-388.
10.1111/jphd.12591
Our ref: RO816
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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 | 2023
Bourassa, Kyle J.; Caspi, Avshalom; Brennan, Grace M.; Hall, Katherine S.; Harrington,
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Psychosomatic Medicine, 2023, 85(5), 389-396.
10.1097/psy.0000000000001197
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Our ref: RO812
Objective Stress and stressful events are associated with poorer health; however, there are multiple ways to conceptualize and measure stress and stress responses. One physiological mechanism through which stress could result in poorer health is accelerated biological aging. This study tested which types of stress were associated with accelerated biological aging in adulthood. Methods Studying 955 participants from the Dunedin Longitudinal Study, we tested whether four types of stress assessed from ages 32 to 45 years—perceived stress, number of stressful life events, adverse childhood experiences, and posttraumatic stress disorder—were associated with accelerated biological aging. Results Higher levels of all four measures of stress were significantly associated with accelerated aging in separate models. In a combined model, more perceived stress and more stressful life events remained associated with faster aging, and the stress measures explained 6.9% of the variance in aging. The magnitudes of the associations between the four measures of stress and biological aging were comparable to associations for smoking and low education, two established risk factors for accelerated aging. People with high levels of perceived stress, numerous adverse childhood experiences (4+), high stressful life event counts, or posttraumatic stress disorder were aging an additional estimated 2.4 months, 1.1 additional months, 1.4 months, and 1.4 months per year, respectively. Conclusions Assessing stress, particularly perceived stress, could help identify people at risk of accelerated aging. Intervening to treat stress or the health-relevant sequelae of stress could potentially slow the rate at which people are aging, improving their health as they age.
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Social isolation from childhood to mid-adulthood: is there an association with older brain age? | 2023
Lay-Yee, R. Hariri, A. R. Knodt, A. R. Barrett-Young, A. Matthews,
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Psychological Medicine, 2023, 53(16), 7874-7882.
10.1017/s0033291723001964
Our ref: RO808
BACKGROUND: Older brain age - as estimated from structural MRI data - is known to be associated with detrimental mental and physical health outcomes in older adults. Social isolation, which has similar detrimental effects on health, may be associated with accelerated brain aging though little is known about how different trajectories of social isolation across the life course moderate this association. We examined the associations between social isolation trajectories from age 5 to age 38 and brain age assessed at age 45. METHODS: We previously created a typology of social isolation based on onset during the life course and persistence into adulthood, using group-based trajectory analysis of longitudinal data from a New Zealand birth cohort. The typology comprises four groups: 'never-isolated', 'adult-only', 'child-only', and persistent 'child-adult' isolation. A brain age gap estimate (brainAGE) - the difference between predicted age from structural MRI date and chronological age - was derived at age 45. We undertook analyses of brainAGE with trajectory group as the predictor, adjusting for sex, family socio-economic status, and a range of familial and child-behavioral factors. RESULTS: Older brain age in mid-adulthood was associated with trajectories of social isolation after adjustment for family and child confounders, particularly for the 'adult-only' group compared to the 'never-isolated' group. CONCLUSIONS: Although our findings are associational, they indicate that preventing social isolation, particularly in mid-adulthood, may help to avert accelerated brain aging associated with negative health outcomes later in life.
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Life-Course Persistent Antisocial Behavior and Accelerated Biological Aging in a Longitudinal Birth Cohort | 2022
Langevin, S., Caspi, A., Barnes,
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Int J Environ Res Public Health, 2022, 19(21), .
https://doi.org/10.3390/ijerph192114402
Our ref: RO792
Prior research shows that individuals who have exhibited antisocial behavior are in poorer health than their same-aged peers. A major driver of poor health is aging itself, yet research has not investigated relationships between offending trajectories and biological aging. We tested the hypothesis that individuals following a life-course persistent (LCP) antisocial trajectory show accelerated aging in midlife. Trajectories of antisocial behavior from age 7 to 26 years were studied in the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort (N = 1037). Signs of aging were assessed at age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports. First, we tested whether the association between antisocial behavior trajectories and midlife signs of faster aging represented a decline from initial childhood health. We then tested whether decline was attributable to tobacco smoking, antipsychotic medication use, debilitating illnesses in adulthood, adverse exposures in childhood (maltreatment, socioeconomic disadvantage) and adulthood (incarceration), and to childhood self-control difficulties. Study members with a history of antisocial behavior had a significantly faster pace of biological aging by midlife, and this was most evident among individuals following the LCP trajectory (beta, 0.22, 95%CI, 0.14, 0.28, p
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Preparedness for healthy ageing and polysubstance use in long-term cannabis users: a population-representative longitudinal study | 2022
Meier, M.H., Caspi, A., Ambler,
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The Lancet Healthy Longevity, 2022, 3(10), e703-e714.
https://doi.org/10.1016/s2666-7568(22)00201-x
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Our ref: RO789
Background Cannabis is often characterised as a young person’s drug. However, people who began consuming cannabis in the 1970s and 1980s are no longer young and some have consumed it for many years. This study tested the preregistered hypothesis that long-term cannabis users show accelerated biological ageing in midlife and poorer health preparedness, financial preparedness, and social preparedness for old age.
Methods In this longitudinal study, participants comprised a population-representative cohort of 1037 individuals born in Dunedin, New Zealand, between April, 1972, and March, 1973, and followed to age 45 years. Cannabis, tobacco, and alcohol use and dependence were assessed at ages 18 years, 21 years, 26 years, 32 years, 38 years, and 45 years. Biological ageing and health, financial, and social preparedness for old age were assessed at age 45 years. Long-term cannabis users were compared using independent samples t tests with five groups: lifelong cannabis nonusers, long-term tobacco users, long-term alcohol users, midlife recreational cannabis users, and cannabis quitters. In addition, regression analyses tested dose–response associations for continuously measured persistence of cannabis dependence from age 18 years to 45 years, with associations adjusted for sex, childhood socioeconomic status, childhood IQ, low childhood self-control, family substance dependence history, and persistence of alcohol, tobacco, and other illicit drug dependence.
Findings Of 997 cohort members still alive at age 45 years, 938 (94%) were assessed at age 45 years. Long-term cannabis users showed statistically significant accelerated biological ageing and were less equipped to manage a range of later-life health, financial, and social demands than non-users. Standardised mean differences between longterm cannabis users and non-users were large: 0·70 (95% CI 0·46 to 0·94; p<0·0001) for biological ageing, –0·72 (–0·96 to –0·49, p<0·0001) for health preparedness, –1·08 (–1·31 to –0·85; p<0·0001) for financial preparedness, and –0·59 (–0·84 to –0·34, p<0·0001) for social preparedness. Long-term cannabis users did not fare better than long-term tobacco or alcohol users. Tests of dose–response associations suggested that cannabis associations could not be explained by the socioeconomic origins, childhood IQ, childhood self-control, and family substance-dependence history of long-term cannabis users. Statistical adjustment for long-term tobacco, alcohol, and other illicit drug dependence suggested that long-term cannabis users’ tendency toward polysubstance dependence accounted for their accelerated biological ageing and poor financial and health preparedness, although not for their poor social preparedness (β –0·10, 95% CI –0·18 to –0·02; p=0·017).
Interpretation Long-term cannabis users are underprepared for the demands of old age. Although long-term cannabis use appears detrimental, the greatest challenge to healthy ageing is not use of any specific substance, but rather the long-term polysubstance use that characterises many long-term cannabis users. Substance-use interventions should include practical strategies for improving health and building financial and social capital for healthy longevity.
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DunedinPACE: a DNA methylation biomarker of the Pace of Aging | 2022
Belsky, D.W., Caspi, A., Corcoran,
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eLife, 2022, .
https://doi.org/10.7554/eLife.73420
Our ref: RO776
Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).
Methods: We used data from the Dunedin Study 1972–1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named Dunedin-PACE, in five additional datasets.
Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.
Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.
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Association of Treatable Health Conditions During Adolescence With Accelerated Aging at Midlife | 2022
Bourassa, K., Moffitt, T.E., Ambler,
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JAMA Pediatrics , 2022, .
https://doi.org/10.1001/jamapediatrics.2021.6417
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Our ref: RO773
Importance Biological aging is a distinct construct from health; however, people who age quickly are more likely to experience poor health. Identifying pediatric health conditions associated with accelerated aging could help develop treatment approaches to slow midlife aging and prevent poor health in later life.
Objective To examine the association between 4 treatable health conditions in adolescence and accelerated aging at midlife.
Design, Setting, and Participants This cohort study analyzed data from participants in the Dunedin Study, a longitudinal investigation of health and behavior among a birth cohort born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, and followed up until age 45 years. Participants underwent an assessment at age 45 years and had data for at least 1 adolescent health condition (asthma, smoking, obesity, and psychological disorders) and outcome measure (pace of aging, gait speed, brain age, and facial age). Data analysis was performed from February 11 to September 27, 2021.
Exposures Asthma, cigarette smoking, obesity, and psychological disorders were assessed at age 11, 13, and 15 years.
Main Outcomes and Measures The outcome was a midlife aging factor composite score comprising 4 measures of biological aging: pace of aging, gait speed, brain age (specifically, BrainAGE score), and facial age.
Results A total of 910 participants (459 men [50.4%]) met the inclusion criteria, including an assessment at age 45 years. Participants who had smoked daily (0.61 [95% CI, 0.43-0.79] SD units), had obesity (0.82 [95% CI, 0.59-1.06] SD units), or had a psychological disorder diagnosis (0.43 [95% CI, 0.29-0.56] SD units) during adolescence were biologically older at midlife compared with participants without these conditions. Participants with asthma were not biologically older at midlife (0.02 [95% CI, −0.14 to 0.19] SD units) compared with those without asthma. These results remained unchanged after adjusting for childhood risk factors such as poor health, socioeconomic disadvantage, and adverse experiences.
Conclusions and Relevance This study found that adolescent smoking, obesity, and psychological disorder diagnoses were associated with older biological age at midlife. These health conditions could be treated during adolescence to reduce the risk of accelerated biological aging later in life.
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Changes in incisor relationship over the life course - Findings from a cohort study | 2022
Olliver SJ., Broadbent JM., Prasad, S., Cai,
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Journal of Dentistry, 2022, 117 .
https://doi.org/10.1016/j.jdent.2021.103919
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Our ref: RO771
OBJECTIVE: The aim of this longitudinal cohort study was to investigate the changes in incisor relationship over three decades from adolescence to mid-adulthood. MATERIALS AND METHODS: The sample included 1,037 children (48.4% female) born between April 1972 and March 1973 from the longitudinal birth cohort Dunedin Multidisciplinary Health and Development Study. Overjet and overbite values were assessed at age 15 and 45 years and entered in a regression model as outcome variables. Baseline occlusal variables, sex, history of orthodontic treatment, periodontal data recorded at age 38, and self-reported oral parafunction and orthodontic treatment history recorded at age 45 were entered as covariates in the regression analysis. RESULTS: Regression modelling showed that overjet/overbite category (high or low) at age 15 tends to predict overjet/overbite category at age 45, with overjet become slightly larger (around +0.5mm) and overbite slightly lower (-0.5mm) over time. Study members with self-reported tooth clenching had a slighter greater overbite (+0.3mm) at age 45 than those who did not. Additionally, those with signs of periodontal disease at age 38 had a slightly larger overjet (+0.5mm) at age 45 than those without disease. Sex differences were demonstrated with females having 0.6 mm larger overjet, and 0.4 mm overbite at age 45. CONCLUSIONS: Overall, overjet values tend to be higher during mid-adulthood than during adolescence, while the converse is true for overbite. There appears to be a degree of sexual dimorphism in overjet and overbite values later in life. CLINICAL SIGNIFICANCE: Incisor relationships change during the life course and are related to ageing, sex, periodontal health, and parafunctional habits. Clinicians and educators should be aware of these changes when making treatment decisions that alter incisor relationship.
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Are macular drusen in midlife a marker of accelerated biological ageing? | 2021
Graham A Wilson, Kirsten Cheyne, Sandhya Ramrakha, Antony Ambler, Gavin SW Tan,
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Clinical and Experimental Optometry, 2021, 1-6.
https://doi.org/10.1080/08164622.2021.2012428
Our ref: RO770
Clinical relevance: Macular drusen are associated with age-related maculopathy but are not an ocular manifestation or biomarker of systemic ageing.
Background: Macular drusen are the first sign of age-related maculopathy, an eye disease for which age is the strongest risk factor. The aim of this cohort study was to investigate whether macular drusen in midlife – a sign of the earliest stages of age-related macular degeneration (AMD) – are
associated with accelerated biological ageing more generally.
Methods: Members of the long-running Dunedin Multidisciplinary Health and Development Study (hereafter the Dunedin Study, n = 1037) underwent retinal photography at their most recent assessment at the age of 45 years. Images were graded for the presence of AMD using a simplified
scale from the Age-Related Eye Disease Study (AREDS). Accelerated ageing was assessed by (i) a measure of Pace of Ageing defined from a combination of clinical and serum biomarkers obtained at ages 26, 32, 38, and 45 years and (ii) Facial Ageing, defined from photographs obtained at age 38 and 45 years.
Results: Of the 938 participants who participated at the age 45 assessments, 834 had gradable retinal photographs, and of these 165 (19.8%) had macular drusen. There was no significant difference in Pace of Ageing (p = .743) or Facial Ageing (p = .945) among participants with and without macular drusen.
Conclusions: In this representative general population sample, macular drusen in midlife were not associated with accelerated ageing. Future studies tracking longitudinal changes in drusen number and severity at older ages may reveal whether drusen are a biomarker of accelerated ageing.
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Vital personality scores and healthy aging: Life-course associations and familial transmission | 2021
J. Wertz, S. Israel, L. Arseneault, D. W. Belsky, K. J. Bourassa,
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Social Science & Medicine, 2021, 285 .
https://doi.org/10.1016/j.socscimed.2021.114283
Our ref: RO766
Objectives Personality traits are linked with healthy aging, but it is not clear how these associations come to manifest across the life-course and across generations. To study this question, we tested a series of hypotheses about (a) personality-trait prediction of markers of healthy aging across the life-course, (b) developmental origins, stability and change of links between personality and healthy aging across time, and (c) intergenerational transmission of links between personality and healthy aging. For our analyses we used a measure that aggregates the contributions of Big 5 personality traits to healthy aging: a “vital personality” score. Methods Data came from two population-based longitudinal cohort studies, one based in New Zealand and the other in the UK, comprising over 6000 study members across two generations, and spanning an age range from birth to late life. Results Our analyses revealed three main findings: first, individuals with higher vital personality scores engaged in fewer health-risk behaviors, aged slower, and lived longer. Second, individuals’ vital personality scores were preceded by differences in early-life temperament and were relatively stable across adulthood, but also increased from young adulthood to midlife. Third, individuals with higher vital personality scores had children with similarly vital partners, promoted healthier behaviors in their children, and had children who grew up to have more vital personality scores themselves, for genetic and environmental reasons. Conclusion Our study shows how the health benefits associated with personality accrue throughout the life-course and across generations.
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Autistic traits are associated with faster pace of aging: Evidence from the Dunedin study at age 45 | 2021
Mason, D. Ronald, A. Ambler, A. Caspi, A. Houts,
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Autism Research, 2021, .
10.1002/aur.2534
Link to full publication »
Our ref: RO760
Growing evidence indicates that the defining characteristics of autism spectrum disorder (ASD) are distributed throughout the general population; hence, understanding the correlates of aging in people with high autistic traits could shed light on ASD and aging. 915 members of the Dunedin longitudinal birth cohort completed a measure of autistic traits at age 45. A composite measure of the "pace of aging" was derived by tracking the decline in 19 biomarkers across ages 26, 32, 38, and 45 years. Facial age was also assessed. Reports of perceived health were collected from participants themselves, informants, and interviewers. Higher self-reported autistic traits significantly correlated with a faster pace of aging, older facial age, and poorer self-, informant-, and interviewer-rated health. After control for sex, SES and IQ, autistic traits were significantly associated with each variable: pace of aging (beta = 0.09), facial age (beta = 0.08), self- (beta = -0.15), informant (beta = -0.12), and interviewer-rated (beta = -0.17) health. Autistic traits measured at age 45 are associated with faster aging. Participants with high autistic traits appear to be more vulnerable to poor health outcomes, as previously reported for those clinically diagnosed with ASD. Therefore, autistic traits may have important health implications. Replicating these findings in samples of autistic people is needed to identify the mechanism of their effect on aging and physical health to improve outcomes for those with ASD diagnoses or high autistic traits. LAY SUMMARY: The role that autistic traits have in relation to health outcomes has not been investigated. We looked at how physical health and aging (measured with self-reported questions and decline in multiple biological measures) were related to autistic traits (measured with a questionnaire, at age 45). We found that higher autistic traits were associated with poorer reports of physical health, and a faster pace of aging. This suggests that both those with autism and those with higher autistic traits may be more likely to experience poorer health outcomes.
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Association of History of Psychopathology With Accelerated Aging at Midlife | 2021
Wertz, Jasmin, Avshalom Caspi, Antony Ambler, Jonathan Broadbent,
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JAMA Psychiatry, 2021, .
10.1001/jamapsychiatry.2020.4626
Link to full publication »
Our ref: RO757
Importance Individuals with mental disorders are at an elevated risk of developing chronic age-related physical diseases. However, it is not clear whether psychopathology is also associated with processes of accelerated aging that precede the onset of age-related disease.
Objective To test the hypothesis that a history of psychopathology is associated with indicators of accelerated aging at midlife.
Design, Setting, and Participants This prospective cohort study was based on the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort of 1037 individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand. Members were followed up to age 45 years (until April 2019). Data were analyzed from January 6 to December 7, 2020.
Exposures Mental disorders were assessed in 6 diagnostic assessments from ages 18 to 45 years and transformed through confirmatory factor analysis into continuous measures of general psychopathology (p-factor) and dimensions of internalizing, externalizing, and thought disorders (all standardized to a mean [SD] of 100 [15]).
Main Outcomes and Measures Signs of aging (biological pace of aging; declines in sensory, motor, and cognitive functioning; and facial age) were assessed up to age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports.
Results Of the original 1037 cohort participants, 997 were still alive at age 45 years, of whom 938 (94%) were assessed (474 men [50.5%]). Participants who had experienced more psychopathology exhibited a faster pace of biological aging (β, 0.27; 95% CI, 0.21-0.33; P < .01); experienced more difficulties with hearing (β, 0.18; 95% CI, 0.12-0.24; P < .01), vision (β, 0.08; 95% CI, 0.01-0.14; P < .05), balance (β, 0.20; 95% CI, 0.14-0.26; P < .01), and motor functioning (β, 0.19; 95% CI, 0.12-0.25; P < .01); experienced more cognitive difficulties (β, 0.24; 95% CI, 0.18-0.31; P < .01); and were rated as looking older (β, 0.20; 95% CI, 0.14-0.26; P < .01). Associations persisted after controlling for sex, childhood health indicators, maltreatment, and socioeconomic status and after taking into account being overweight, smoking, use of antipsychotic medication, and the presence of physical disease. Tests of diagnostic specificity revealed that associations were generalizable across externalizing, internalizing, and thought disorders.
Conclusions and Relevance In this cohort study, a history of psychopathology was associated with accelerated aging at midlife, years before the typical onset of age-related diseases. This link is not specific to any particular disorder family but generalizes across disorders. Prevention of psychopathology and monitoring of individuals with mental disorders for signs of accelerated aging may have the potential to reduce health inequalities and extend healthy lives.
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Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy | 2021
Maxwell L. Elliott, Avshalom Caspi, Renate M. Houts, Antony Ambler, Jonathan M. Broadbent,
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Nature Aging, 2021, 1 295–308.
https://doi.org/10.1038/s43587-021-00044-4
Link to full publication »
Our ref: RO751
Some humans age faster than others. Variation in biological aging can be measured in midlife, but the implications of this variation are poorly understood. We tested associations between midlife biological aging and indicators of future frailty risk in the Dunedin cohort of 1,037 infants born the same year and followed to age 45. Participants’ ‘Pace of Aging’ was quantified by tracking declining function in 19 biomarkers indexing the cardiovascular, metabolic, renal, immune, dental and pulmonary systems across ages 26, 32, 38 and 45 years. At age 45 in 2019, participants with faster Pace of Aging had more cognitive difficulties, signs of advanced brain aging, diminished sensory–motor functions, older appearances and more pessimistic perceptions of aging. People who are aging more rapidly than same-age peers in midlife may prematurely need supports to sustain independence that are usually reserved for older adults. Chronological age does not adequately identify need for such supports.
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Childhood self-control forecasts the pace of midlife aging and preparedness for old age | 2021
Richmond-Rakerd, L. S. Caspi, A. Ambler, A. d'Arbeloff, T. de Bruine,
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PNAS, 2021, 118(3), .
https://doi.org/10.1073/pnas.2010211118
Link to full publication »
Our ref: RO748
The ability to control one's own emotions, thoughts, and behaviors in early life predicts a range of positive outcomes in later life, including longevity. Does it also predict how well people age? We studied the association between self-control and midlife aging in a population-representative cohort of children followed from birth to age 45 y, the Dunedin Study. We measured children's self-control across their first decade of life using a multi-occasion/multi-informant strategy. We measured their pace of aging and aging preparedness in midlife using measures derived from biological and physiological assessments, structural brain-imaging scans, observer ratings, self-reports, informant reports, and administrative records. As adults, children with better self-control aged more slowly in their bodies and showed fewer signs of aging in their brains. By midlife, these children were also better equipped to manage a range of later-life health, financial, and social demands. Associations with children's self-control could be separated from their social class origins and intelligence, indicating that self-control might be an active ingredient in healthy aging. Children also shifted naturally in their level of self-control across adult life, suggesting the possibility that self-control may be a malleable target for intervention. Furthermore, individuals' self-control in adulthood was associated with their aging outcomes after accounting for their self-control in childhood, indicating that midlife might offer another window of opportunity to promote healthy aging.
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Intimate partner violence and lower relationship quality are associated with faster biological aging | 2020
Bourassa, K. J. Caspi, A. Harrington, H. Houts, R. Poulton,
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Psychology and Aging, 2020, 35(8), 1127-1139.
http://dx.doi.org/10.1037/pag0000581
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Our ref: RO747
The characteristics of people's relationships have relevance to health-high quality romantic relationships are associated with improved health whereas intimate partner violence is associated with poorer health. Recently, increased attention has been focused on the biological processes underpinning these associations. A geroscience approach-examining whether close relationship characteristics are associated with biological aging-would complement previous research focused on individual disease pathways. This study used participants from the Dunedin Study (N = 974) to investigate relationship characteristics and biological aging across almost 20 years, from age 26 to 45. Being involved in romantic relationships was associated with slower biological aging, beta = -0.12, p < .001. This difference represented 2.9 years of aging over the two decades. Greater relationship quality was also associated with slower biological aging, beta = -0.19, p < .001, whereas higher levels of partner violence were associated with faster biological aging, beta = 0.25, p < .001. A 1 SD difference in these characteristics was associated with a difference of 1.0 and 1.3 years of aging over the two decades, respectively. Secondary analyses suggested that experiencing violence from a partner was more strongly associated with biological aging than perpetrating violence, and that the experience of physical violence was more strongly associated with aging than psychological violence. These findings suggest that the characteristics of romantic relationships have relevance for biological aging in midlife. Interventions designed to increase relationship quality and decrease partner violence could reduce future morbidity and early mortality by slowing people's biological aging. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Is cardiovascular fitness associated with structural brain integrity in midlife? Evidence from a population-representative birth cohort study | 2020
d'Arbeloff, T., Cooke, M., Knodt,
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Aging, 2020, 12(20), .
https://doi.org/10.18632/aging.104112
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Our ref: RO744
Improving cardiovascular fitness may buffer against age-related cognitive decline and mitigate dementia risk by staving off brain atrophy. However, it is unclear if such effects reflect factors operating in childhood (neuroselection) or adulthood (neuroprotection). Using data from 807 members of the Dunedin Study, a population-representative birth cohort, we investigated associations between cardiovascular fitness and structural brain integrity at age 45, and the extent to which associations reflected possible neuroselection or neuroprotection by controlling for childhood IQ. Higher fitness, as indexed by VO2Max, was not associated with average cortical thickness, total surface area, or subcortical gray matter volume including the hippocampus. However, higher fitness was associated with thicker cortex in prefrontal and temporal regions as well as greater cerebellar gray matter volume. Higher fitness was also associated with decreased hippocampal fissure volume. These associations were unaffected by the inclusion of childhood IQ in analyses. In contrast, a higher rate of decline in cardiovascular fitness from 26 to 45 years was not robustly associated with structural brain integrity. Our findings are consistent with a neuroprotective account of adult cardiovascular fitness but suggest that effects are not uniformly observed across the brain and reflect contemporaneous fitness more so than decline over time
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Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm | 2020
Daniel W Belsky, Avshalom Caspi, Louise Arseneault, Andrea Baccarelli, David L Corcoran,
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eLife Epidemiology and Global Health, 2020, .
https://doi.org/10.7554/eLife.54870
Our ref: RO738
Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is sensitive to variation in pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972–1973. Rates of change in each biomarker over ages 26–38 years were composited to form a measure of aging-related decline, termed Pace-of-Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging.
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Association between elevated suPAR, a new biomarker of inflamation, and accelerated aging | 2020
Line Jee Hartmann Rasmussen, Avshalom Caspi, Antony Ambler, Andrea Danese, Maxwell Elliott,
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The Journals of Gerontology: Series A, 2020, .
https://doi.org/10.1093/gerona/glaa178
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Our ref: RO732
Background
To understand and measure the association between chronic inflammation, aging, and age-related diseases, broadly applicable standard biomarkers of systemic chronic inflammation are needed. We tested whether elevated blood levels of the emerging chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR) were associated with accelerated aging, lower functional capacity, and cognitive decline.
Methods
We used data from the Dunedin Study, a population-representative 1972–1973 New Zealand birth cohort (n=1037) that has observed participants to age 45 years. Plasma suPAR levels were analyzed at ages 38 and 45 years. We performed regression analyses adjusted for sex, smoking, C-reactive protein, and current health conditions.
Results
Of 997 still-living participants, 875 (88%) had plasma suPAR measured at age 45. Elevated suPAR was associated with accelerated pace of biological aging across multiple organ systems, older facial appearance, and with structural signs of older brain age. Moreover, participants with higher suPAR levels had greater decline in physical function and cognitive function from childhood to adulthood compared to those with lower suPAR levels. Finally, improvements in health habits between ages 38 and 45 (smoking cessation or increased physical activity) were associated with less steep increases in suPAR levels over those years.
Conclusions
Our findings provide initial support for the utility of suPAR in studying the role of chronic inflammation in accelerated aging and functional decline.
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Psychiatry’s Opportunity to Prevent the Rising Burden of Age-Related Disease | 2019
Terrie E. Moffitt, Avshalom Caspi
JAMA Psychiatry, 2019, 76(5), 461–462.
https://doi.org/10.1001/jamapsychiatry.2019.0037
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Our ref: RO755
Three demographic trends are colliding to form a perfect storm: the postretirement portion of the population is swelling, the human life span is lengthening, and the birth rate is dropping. The result is that the balance of young to old in the population is shifting, leaving fewer young workers to drive the economy and pay taxes to support aging citizens. These 3 trends mean more stress for the young and less support for the old, bringing 2 opportunities for the mental health field. First, an opportunity to prevent disability among young people, which would enhance their well-being and capacity to shoulder the burden of the dependent older population. Young people tend to be physically healthy but can experience behavioral problems, emotional problems, substance abuse, and cognitive impairments. These conditions respond to mental health treatments. Second, an opportunity to prevent ill health among older people, which would reduce the burden of age-related disability. Here, we argue that psychiatry is well situated to prevent disability among older people by doing something it does well: treat young people. Risk-prediction research shows that the same people who have poor mental and cognitive health while young tend to have age-related diseases years later.1,2 Moreover, the timing is right. Mental disorders peak in adolescence and young adulthood, whereas noninfectious diseases peak in midlife and neurodegenerative conditions peak in late life.
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Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth cohort | 2019
Elliott, M.L. Belsky, D.W., Knodt, A.R.,
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Molecular Psychiatry, 2019, .
https://doi.org/10.1038/s41380-019-0626-7
Our ref: RO733
An individual’s brainAGE is the difference between chronological age and age predicted from machine-learning models of brain-imaging data. BrainAGE has been proposed as a biomarker of age-related deterioration of the brain. Having an older brainAGE has been linked to Alzheimer’s, dementia, and mortality. However, these findings are largely based on crosssectional associations which can confuse age differences with cohort differences. To illuminate the validity of brainAGE as a biomarker of accelerated brain aging, a study is needed of a large cohort all born in the same year who nevertheless vary on brainAGE. In the Dunedin Study, a population-representative 1972–73 birth cohort, we measured brainAGE at age 45 years, as well as the pace of biological aging and cognitive decline in longitudinal data from childhood to midlife (N = 869). In this cohort, all chronological age 45 years, brainAGE was measured reliably (ICC = 0.81) and ranged from 24 to 72 years. Those with older midlife brainAGEs tended to have poorer cognitive function in both adulthood and childhood, as well as impaired brain health at age 3. Furthermore, those with older brainAGEs had an accelerated pace of biological aging, older facial appearance, and early signs of cognitive decline from childhood to midlife. These findings help to validate brainAGE as a potential surrogate biomarker for midlife intervention studies that seek to measure dementia-prevention efforts in midlife. However, the findings also caution against the assumption that brainAGE scores represent only age-related deterioration of the brain as they may also index central nervous system variation present since childhood.
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Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing? | 2018
Belsky, D. W. Moffitt, T.E. Cohen, A.A. Corcoran, D. L. Levine,
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American Journal of Epidemiology, 2018, 187(6), 1220-1230.
http://dx.doi.org/10.1093/aje/kwx346
Our ref: RO700
The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such “gero-protective” therapies in humans, outcome measures are needed that can assess extension of disease-free lifespan. This need has spurred development of different methods to quantify biological aging. But different methods have not been systematically compared in the same humans. We implemented seven methods to quantify biological aging using repeated-measures physiological and genomic data in 964 middle-aged humans in the Dunedin Study. We studied telomere-length and erosion, three epigenetic-clocks and their ticking rates, and three biomarker-composites, 11 measures in total. Contrary to expectation, we found low agreement between different measures of biological aging. We next compared associations between biological aging measures and outcomes gero-protective therapies seek to modify: physical functioning, cognitive decline, and subjective signs of aging, including aged facial appearance. The 71-CpG epigenetic clock and biomarker composites were consistently related to these aging-related outcomes. However, effect-sizes were modest. Results suggests that various proposed approaches to quantifying biological aging may not measure the same aspects of the aging process. Further systematic evaluation and refinement of measures of biological aging is needed to furnish outcomes for geroprotector trials.
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Impact of early personal-history characteristics on the Pace of Aging: implications for clinical trials of therapies to slow aging and extend healthspan | 2017
Belsky, D. W., Caspi, A., Cohen,
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Aging Cell, 2017, 16(4), 644-651.
Link to full publication »
Our ref: RO699
Therapies to extend healthspan are poised to move from laboratory animal models to human clinical trials. Translation from mouse to human will entail challenges, among them the multifactorial heterogeneity of human aging. To inform clinical trials about this heterogeneity, we report how humans’ pace of biological aging relates to personal-history characteristics. Because geroprotective therapies must be delivered by midlife to prevent age-related disease onset, we studied young-adult members of the Dunedin Study 1972–73 birth cohort (n = 954). Cohort members’ Pace of Aging was measured as coordinated decline in the integrity of multiple organ systems, by quantifying rate of decline across repeated measurements of 18 biomarkers assayed when cohort members were ages 26, 32, and 38 years. The childhood personal-history characteristics studied were known predictors of age-related disease and mortality, and were measured prospectively during childhood. Personal-history characteristics of familial longevity, childhood social class, adverse childhood experiences, and childhood health, intelligence, and self-control all predicted differences in cohort members’ adulthood Pace of Aging. Accumulation of more personal-history risks predicted faster Pace of Aging. Because trials of anti-aging therapies will need to ascertain personal histories retrospectively, we replicated results using cohort members’ retrospective personal-history reports made in adulthood. Because many trials recruit participants from clinical settings, we replicated results in the cohort subset who had recent health system contact according to electronic medical records. Quick, inexpensive measures of trial participants’ early personal histories can enable clinical trials to study who volunteers for trials, who adheres to treatment, and who responds to anti-aging therapies.
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The Longitudinal Study of Aging in Human Young Adults: Knowledge Gaps and Research Agenda | 2017
Moffitt, T. E., Belsky, D. W., Danese,
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J Gerontol A Biol Sci Med Sci, 2017, 72(2), 210-215.
DOI: 10.1093/gerona/glw191
Our ref: RO695
To prevent onset of age-related diseases and physical and cognitive decline, interventions to slow human aging and extend health span must eventually be applied to people while they are still young and healthy. Yet most human aging research examines older adults, many with chronic disease, and little is known about aging in healthy young humans. METHOD: This article explains how this knowledge gap is a barrier to extending health span and puts forward the case that geroscience should invest in researching the pace of aging in young adults. As one illustrative example, we describe an initial effort to study the pace of aging in a young-adult birth cohort by using repeated waves of biomarkers collected across the third and fourth decades to quantify the pace of coordinated physiological deterioration across multiple organ systems (eg, pulmonary, periodontal, cardiovascular, renal, hepatic, metabolic, and immune function). RESULTS: Findings provided proof of principle that it is possible to quantify individual variation in the pace of aging in young adults still free of age-related diseases. CONCLUSIONS: This article articulates research needs to improve longitudinal measurement of the pace of aging in young people, to pinpoint factors that slow or speed the pace of aging, to compare pace of aging against genomic clocks, to explain slow-aging young adults, and to apply pace of aging in preventive clinical trials of antiaging therapies. This article puts forward a research agenda to fill the knowledge gap concerning lifelong causes of aging.
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