Quantification of the pace of biological aging in humans through a blood test, The DunedinPoAm DNA methylation algorithm
- Columbia University Mailman School of Public Health, United States
- Duke University, United States
- Institute of Psychiatry, Kings College London, United Kingdom
- University of Exeter, United Kingdom
- Duke University, United Kingdom
- University of Otago, New Zealand
- Harvard TH Chan School of Public Health, United States
- Boston University School of Medicine, United States
Abstract
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.
Data availability
Datasets are available from the data owners. Data from the Dunedin and E-Risk Study can be accessed through agreement with the Study investigators. Instructions are available at https://sites.google.com/site/moffittcaspiprojects/. The data access application form can be downloaded here: https://sites.google.com/site/moffittcaspiprojects/forms-for-new-projects/concept-paper-templateData from the Understanding Society Study is available through METADAC at https://www.metadac.ac.uk/ukhls/. All details are on the Metadac website (https://www.metadac.ac.uk/data-access-through-metadac/). The data access application form can be found here https://www.metadac.ac.uk/files/2019/02/v2.41-UKHLS-METADAC-application-form-2019-2hak8bv.docx Data from the Normative Aging Study were obtained from the Study investigators. Data are accessible through dbGaP, accession phs000853.v1.p1. CALERIE Data are available for download from the CALERIE Biorepository at https://calerie.duke.edu/. Details are on the website here: https://calerie.duke.edu/samples-data-access-and-analysis
Article and author information
Author details
Line J H Rasmussen
Funding
Medical Research Council (MR/P005918/1)
- Terrie E Moffitt
Medical Research Council (G1002190)
- Terrie E Moffitt
National Institute on Aging (AG032282)
- Terrie E Moffitt
National Institute on Aging (U24AG047121)
- William E Kraus
National Institute on Aging (R01AG061378)
- Daniel W W Belsky
National Institute on Aging (R21AG054846)
- Daniel W W Belsky
National Institute of Child Health and Development (HD077482)
- Avshalom Caspi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Research participants provided informed consent for participation in the included studies. Approval for this study was provided by the institutional review boards of the New Zealand Ministry of Health Health and Disability Ethics Committee (17/STH/25/AM05), Duke University (protocols 1604 and 0414B0360), Duke University Medical Center (00078391) and Columbia University Irving Medical Center (protocols AAAS2948 and AAAQ8739).
Copyright
© 2020, Belsky et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Quantification of the pace of biological aging in humans through a blood test, The DunedinPoAm DNA methylation algorithm
eLife 9:e54870.
https://doi.org/10.7554/eLife.54870
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