eLife (May 2020)
Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm
- Daniel W Belsky,
- Avshalom Caspi,
- Louise Arseneault,
- Andrea Baccarelli,
- David L Corcoran,
- Xu Gao,
- Eiliss Hannon,
- Hona Lee Harrington,
- Line JH Rasmussen,
- Renate Houts,
- Kim Huffman,
- William E Kraus,
- Dayoon Kwon,
- Jonathan Mill,
- Carl F Pieper,
- Joseph A Prinz,
- Richie Poulton,
- Joel Schwartz,
- Karen Sugden,
- Pantel Vokonas,
- Benjamin S Williams,
- Terrie E Moffitt
Affiliations
- Daniel W Belsky
- ORCiD
- Department of Epidemiology, Columbia University Mailman School of Public Health, New York, United States; Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, United States
- Avshalom Caspi
- Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, United Kingdom; Department of Psychology and Neuroscience, Duke University, Durham, United States; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, United States; Center for Genomic and Computational Biology, Duke University, Durham, United States
- Louise Arseneault
- Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, United Kingdom
- Andrea Baccarelli
- Laboratory of Precision Environmental Health, Mailman School of Public Health, Columbia University, New York, United States
- David L Corcoran
- Center for Genomic and Computational Biology, Duke University, Durham, United States
- Xu Gao
- Laboratory of Precision Environmental Health, Mailman School of Public Health, Columbia University, New York, United States
- Eiliss Hannon
- University of Exeter Medical School, College of Medicine and Health, Exeter, United Kingdom
- Hona Lee Harrington
- Department of Psychology and Neuroscience, Duke University, Durham, United States
- Line JH Rasmussen
- ORCiD
- Department of Psychology and Neuroscience, Duke University, Durham, United States; Clinical Research Centre, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark
- Renate Houts
- Department of Psychology and Neuroscience, Duke University, Durham, United States
- Kim Huffman
- Duke Molecular Physiology Institute, Duke University, Durham, United States; Duke University Center for the Study of Aging, Duke University, Durham, United States
- William E Kraus
- Duke Molecular Physiology Institute, Duke University, Durham, United States; Duke University Center for the Study of Aging, Duke University, Durham, United States
- Dayoon Kwon
- Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, United States
- Jonathan Mill
- University of Exeter Medical School, College of Medicine and Health, Exeter, United Kingdom
- Carl F Pieper
- Duke University Center for the Study of Aging, Duke University, Durham, United States; Department of Biostatistics, Duke University School of Medicine, Durham, United States
- Joseph A Prinz
- Center for Genomic and Computational Biology, Duke University, Durham, United States
- Richie Poulton
- Department of Psychology and Dunedin Multidisciplinary Health and Development Research Unit, University of Otago, Otago, New Zealand
- Joel Schwartz
- Department of Environmental Health Sciences, Harvard TH Chan School of Public Health, Boston, United States
- Karen Sugden
- Department of Psychology and Neuroscience, Duke University, Durham, United States
- Pantel Vokonas
- Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Department of Medicine, Boston University School of Medicine, Boston, United States
- Benjamin S Williams
- Department of Psychology and Neuroscience, Duke University, Durham, United States
- Terrie E Moffitt
- Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, United Kingdom; Department of Psychology and Neuroscience, Duke University, Durham, United States; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, United States; Center for Genomic and Computational Biology, Duke University, Durham, United States
- DOI
- https://doi.org/10.7554/eLife.54870
- Journal volume & issue
-
Vol. 9
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.
Keywords
