Evidence map›Paper›PMID 41987221›Full record

ArticleBMC medicine2026

Epigenetic aging markers in the association between frailty and mortality among U.S. adults.

May A Beydoun, Nicole Noren Hooten, Hind A Beydoun, Michael F Georgescu, Jack Tsai, Michele K Evans, Alan B Zonderman

Abstract read
In one paragraph

Article in BMC medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

May A BeydounLaboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA. baydounm@mail.nih.gov.
Nicole Noren HootenLaboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA.ORCID 0000-0002-1683-3838
Hind A BeydounVA National Center On Homelessness Among Veterans, U.S. Department of Veterans Affairs, Washington, DC, 20420, USA.
Michael F GeorgescuLaboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA.
Jack TsaiVA National Center On Homelessness Among Veterans, U.S. Department of Veterans Affairs, Washington, DC, 20420, USA.
Michele K Evans *Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA.
Alan B Zonderman *Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA.

Funding

Healthy Aging Neighborhoods of Diversity Across LifespanZ01AG000513 · NIA · NATIONAL INSTITUTE ON AGING · PI EVANS, MICHELE K · 2001 to 2008
$6.8M
Intramural NIH HHS Z01 AG000513Intramural Research Program of the National Institutes of Health (NIH) AG000513NIH Department of Health and Human Services AG000513
6 · The paper itself

Abstract

backgroundFrailty reflects diminished physiological reserve and increased vulnerability to adverse health outcomes. It has been linked to biological aging, including epigenetic age acceleration (EAA), a DNA methylation-based marker of aging, but the extent to which EAA accounts for the frailty-mortality association remains unclear.

methodsWe analyzed three U.S. cohorts-NHANES (1999-2002), HRS (2016), and HANDLS (2004-2009)-with mortality follow-up through 2019-2022. Frailty was defined using harmonized adaptations of the Fried phenotype and FRAIL scale. EAA was derived from five epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, DunedinPoAm). Additive Bayesian networks, Cox proportional hazards models, and counterfactual four-way decomposition were used to assess potential mediation and moderation of the frailty-mortality association by EAA, adjusting for age, sex, race/ethnicity, and socioeconomic status.

resultsFrailty was strongly associated with higher all-cause mortality in NHANES and HRS. GrimAge and DunedinPoAm showed the strongest mediation. In NHANES, GrimAge accounted for 33% (p < 0.001) and DunedinPoAm mediated 17% (p = 0.006) of the association. In HRS, DunedinPoAm mediated 9% (p = 0.040) and GrimAge 16% (p = 0.020). Other clocks showed limited mediation. HANDLS findings were consistent. Higher socioeconomic status was associated with slower aging and lower frailty risk. Female sex was inversely associated with multiple epigenetic clocks but positively associated with frailty.

conclusionsEpigenetic aging, particularly GrimAge and DunedinPoAm, may explain part of the frailty-mortality association, supporting a role for biological aging pathways linking frailty to mortality.

Indexed as

AgingEpigenesis, GeneticFrailtyMortalityAgedAged, 80 and overDNA MethylationFemaleHumansMaleUnited StatesAdditive Bayesian NetworksBiological agingEpigenetic clocksFrailtyMortality

Identifiers

PMID41987221
PMCPMC13192009

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.