DunedinPACE, a DNA methylation biomarker of the pace of aging.
DNA methylation
aging
biological aging
biomarker
epidemiology
epigenetic
epigenetics
genetics
genomics
gerontology
geroscience
global health
healthspan
methylation
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
14 01 2022
14 01 2022
Historique:
received:
27
08
2021
accepted:
13
12
2021
pubmed:
15
1
2022
medline:
25
2
2022
entrez:
14
1
2022
Statut:
epublish
Résumé
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). 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. 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. DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience. This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.
Sections du résumé
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.
Identifiants
pubmed: 35029144
doi: 10.7554/eLife.73420
pii: 73420
pmc: PMC8853656
doi:
pii:
Substances chimiques
Biomarkers
0
Banques de données
dbGaP
['phs000853.v1.p1', 'phs000007.v32.p13']
GEO
['GSE55763']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : HHSN268201500001C
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD077482
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC25195
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG032282
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES009089
Pays : United States
Organisme : Medical Research Council
ID : MR/P005918/1
Pays : United Kingdom
Organisme : NIEHS NIH HHS
ID : R01 ES025225
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES021733
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061378
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500001I
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG066887
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES027747
Pays : United States
Organisme : Medical Research Council
ID : G1002190
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : 75N92019D00031
Pays : United States
Organisme : Medical Research Council
ID : MR/N01104X/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Déclaration de conflit d'intérêts
DB, AC, DC, KS, RP, TM is listed as an inventor on a Duke University and University of Otago invention that was licensed to a commercial entity, LA, AB, KC, XG, EH, HH, RH, MK, DK, JM, JS, PV, CW, BW No competing interests declared
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