DunedinPACE, a DNA Methylation Biomarker of the Pace of Aging

Overview

Journal Elife

Specialty Biology

Date 2022 Jan 14

PMID 35029144

Authors

Daniel W Belsky

Avshalom Caspi

David L Corcoran

Karen Sugden

Richie Poulton

Louise Arseneault

Andrea Baccarelli

Kartik Chamarti

Xu Gao

Eilis Hannon

Hona Lee Harrington

Renate Houts

Meeraj Kothari

Dayoon Kwon

Jonathan Mill

Joel Schwartz

Pantel Vokonas

Cuicui Wang

Benjamin S Williams

Terrie E Moffitt

Affiliations

Soon will be listed here.

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 1972-1973 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.

Funding: This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.

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