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

Biological age is increased by stress and restored upon recovery

“…Another recently reported second generation approach, called DunedinPACE, uses longitudinal phenotypic training data to produce a measure of the rate of biological aging. 16,17 DNAm clocks have excellent predictive ability and are responsive to known anti-aging/lifespan extending interventions such as caloric restriction. 11 Although mechanistic questions on the nature of DNAm clocks remain, these clocks represent the current gold standard aging biomarker and are now widely utilized in the aging field, including in human clinical trials.…”

Analyzing Corin–BNP–NEP Protein Pathway Revealing Differential Mechanisms in AF-Related Ischemic Stroke and No AF-Related Ischemic Stroke

“…Biological aging is the gradual, progressive decline in system integrity that causes morbidity and disability ( Field et al, 2018 ; Belsky et al, 2022 ). Field et al (2018) and Belsky et al (2020 , 2022) quantitated the pace of biological aging from a DNAm blood test. The vascular stiffness of the elderly population increases with aging.…”

“…Epigenetics, specifically DNA methylation (DNAm), is linked to aging ( Day et al, 2013 ; Horvath, 2013 ; Tharakan et al, 2020 ). DNAm is the most abundant epigenetic marker in the human genome for controlling gene expression ( Belsky et al, 2022 ). It usually occurs in CpG islands and is mostly in the proximal promoter region of the human genome, which modifies an individual’s biological function by regulating gene expression or genome sequence stability ( Deng et al, 2019 ).…”

DNAmFitAge: Biological Age Indicator Incorporating Physical Fitness

“…These are collectively known as epigenetic clocks, and a large body of literature demonstrates these clocks predict lifespan [27, 28], are associated with age-related conditions [28-30], and are reflective of one’s biological age [27, 31]. Second, prediction of aging-related morbidity, disability, and mortality by DNAm biomarkers is enhanced by the incorporation of physiological data into prediction algorithms [27, 28, 32]. This suggests utility in including physical fitness in DNAm biomarkers, however, current DNAm biomarkers do not use fitness parameters in their construction.…”

“…Second, prediction of aging-related morbidity, disability, and mortality by DNAm biomarkers is enhanced by the incorporation of physiological data into prediction algorithms [27,28,32]. This suggests utility in including physical fitness in DNAm biomarkers, however, current DNAm biomarkers do not use fitness parameters in their construction.…”