Quantification of the pace of biological aging in humans through a blood test: The DunedinPoAm DNA methylation algorithm
Year: 2020
Type: preprint
Abstract: 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 to serve 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 the pace of biological aging among individuals born the same year. We first modeled longitudinal change in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in the Dunedin birth cohort. Rates of change in each biomarker 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 analyses showed DunedinPoAm was associated with functional decline in the Dunedin Study and more advanced biological age in the Understanding Society Study, predicted chronic disease and mortality in the Normative Aging Study, was accelerated by early-life adversity in the E-risk Study, and DunedinPoAm prediction was disrupted by caloric restriction in the CALERIE trial. DunedinPoAm generally outperformed epigenetic clocks. Findings provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging.
Authors: DW Belsky, A Caspi, L Arseneault, A Baccarelli, D Corcoran, X Gao, E Hannon, HL Harrington, LJH Rasmussen, R Houts, K Huffman, WE Kraus, D Kwon, J Mill, CF Pieper, J Prinz, R Poulton, J Schwartz, K Sugden, P Vokonas, BS Williams, TE Moffitt
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, North Carolina Biotechnology Center, American Asthma Foundation, University of Essex, Wellcome Trust, Understanding Society, Ministry of Business, Innovation and Employment, Jacobs Foundation, Medical Research Council, Economic and Social Research Council, National Institute of Environmental Health Sciences
Awards: G1049901796, G1151036099, G1289651063, G1649589871, G1748805038, G2039281854, META-DAC - Managing Ethico-social and Technical issues and Administration of Data Access Committee, G2256057897, G2462977380, G4036427723, G412938763, G4160101343, G4558443914, G4907327099, Circulating microRNAs in Extracellular Vesicles, Air Particulate Pollution, and Lung Function in an Aging Cohort, Molecular and Epigenetic Mitochondriomics of Air Particles, Lead and Cognition, G5701737369, Air Particulate, Metals, and Cognitive Performance in an Aging Cohort- Roles of Circulating Extracellular Vesicles and Non-coding RNAs, G6637449936, METADAC, Midlife Pace of Aging in the Dunedin Study, G7638463748, G78481483, How can biomarkers and genetics improve our understanding of society and health?, G8877605831, G8968736666, Center for Environmental Health in Northern Manhattan
OpenAlex ID: W3004496550