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Cited by 1,083Epigenetics and DNA MethylationGenetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and Senescence

DunedinPACE, a DNA methylation biomarker of the pace of aging

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Belsky, Daniel W, Caspi, Avshalom, Corcoran, David L, Sugden, Karen, Poulton, Richie, Arseneault, Louise, Baccarelli, Andrea, Chamarti, Kartik +12 more·2022·eLife
DOI 10.7554/elife.73420PMC PMC8853656

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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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  • DunedinPACE is among the most sensitive indicators of biological aging in most studies.

    “The DunedinPACE measure is among the most sensitive indicator of biological aging in most studies, so this was unexpected (Belsky et al., 2022).”

    From Grandparent Caregiving and Epigenetic Aging among Midlife and Older Adults in the United States (2026) · cites this paper as Belsky et al., 2022

    The Results sections on functional decline and on morbidity, disability, and mortality report that DunedinPACE’s effect sizes were similar to or larger than those of other DNA-methylation measures tested. That supports calling it one of the stronger indicators in this paper’s comparisons, but does not establish that it is among the most sensitive in “most studies” generally. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Belsky, D. W., Caspi, A., Corcoran, D. L., Sugden, K., Poulton, R., Arseneault, L., Baccarelli, A., Chamarti, K., Gao, X., Hannon, E., Harrington, H. L., Houts, R., Kothari, M., Kwon, D., Mill, J., Schwartz, J., Vokonas, P., Wang, C., Williams, B. S., & Moffitt, T. E.
Affiliations
  • Columbia University (US)
  • Duke University (US)
  • University of Otago (NZ)
  • King's College London (GB)
  • Peking University (CN)
  • University of Exeter (GB)
  • Harvard University (US)
  • VA Boston Healthcare System (US)
Corresponding author
Belsky, Daniel W
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2022-01-14
Volume
11
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.73420
PMC
PMC8853656
OpenAlex
W4205358347
Cited by
1,083
References
6
Citations by year
2026: 361 · 2025: 307 · 2024: 244 · 2023: 137 · 2022: 33 · 2021: 1
FWCI
58.97
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Research Portal (King's College London) (submittedVersion, cc-by)
  • Open Research Exeter (University of Exeter) (submittedVersion, public-domain)
Funders
  • National Institute on Aging (AG032282, AG066887, AG061378)
  • Medical Research Council (MR/P005918/1)
  • New Zealand Health Research Council (16-604)
  • New Zealand Ministry of Business, Innovation and Employment
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Keywords
DunedinPACE, pace of aging, DNA methylation biomarkers, epigenetic clocks, GrimAge, biological aging, geroprotective interventions, childhood adversity, morbidity, disability, mortality, test-retest reliability
MeSH terms
Epigenome, Adolescent, Aging, Child, Child, Preschool, Female, Humans, Male, New Zealand, Cohort Studies, Biomarkers, DNA Methylation, Epigenesis, Genetic

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