@article{d23d869f680d4dc5b7b200a3323710af,
title = "DunedinPACE, a DNA methylation biomarker of the pace of aging",
abstract = "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 1972-3 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 DunedinPACE, 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.",
keywords = "General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience",
author = "Belsky, {Daniel W} and Avshalom Caspi and Corcoran, {David L} and Karen Sugden and Richie Poulton and Louise Arseneault and Andrea Baccarelli and Kartik Chamarti and Xu Gao and Eilis Hannon and Harrington, {Hona Lee} and Renate Houts and Meeraj Kothari and Dayoon Kwon and Jonathan Mill and Joel Schwartz and Pantel Vokonas and Cuicui Wang and Williams, {Benjamin S} and Moffitt, {Terrie E}",
note = "Funding Information: The E-Risk Study is supported by the UK Medical Research Council (grant G1002190), the US National Institute of Child Health and Development (grant HD077482), and the Jacobs Foundation. The generation of DNA methylation data was supported by the American Asthma Foundation. Funding Information: This work used a high-performance computing facility partially supported by grant 2016-IDG-1013 (HARDAC+: Reproducible HPC for Next-generation Genomics{"}) from the North Carolina Biotechnology Center. Funding Information: Understanding Society data come from The UK Household Longitudinal Study, which is led by the Institute for Social and Economic Research at the University of Essex and funded by the Economic and Social Research Council (ES/M008592/1). Information on how to access the data can be found on the Understanding Society website https://www.understandingsociety.ac.uk/. Funding Information: The Dunedin Multidisciplinary Health and Development Research Unit is supported by the New Zealand Health Research Council Programme Grant (16-604), and the New Zealand Ministry of Business, Innovation and Employment (MBIE). We thank the Dunedin Study members, Unit research staff, and Study founder Phil Silva. Funding Information: This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1. Funding Information: Data governance was provided by the METADAC data access committee, funded by ESRC, Wellcome, and MRC (2015-2018: MR/N01104X/1; 2018-2020: ES/S008349/1) The Normative Aging Study is supported by the National Institute of Environmental Health Sciences (grants P30ES009089, R01ES021733, R01ES025225, and R01ES027747). The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts. Funding Information: Funding. This research was supported by US-National Institute on Aging grants AG032282, Funding Information: AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1. Funding Information: The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195, HHSN268201500001I and 75N92019D00031). This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or NHLBI. Publisher Copyright: {\textcopyright} 2022, eLife Sciences Publications Ltd. All rights reserved.",
year = "2022",
month = jan,
doi = "10.7554/elife.73420",
language = "English",
volume = "11",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications, Ltd",
}