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 | 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
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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