Evidence map›Paper›PMID 42477337›Full record

Articlenpj aging2026

How epigenetic clocks tick: unpacking the black box by deciphering biological pathways and transcriptomic signatures of accelerated aging.

Thalida Em Arpawong, Steve Cole, Harshanna Badhesha, Jung Ki Kim, Christopher R Beam, Eric T Klopack, Kimberly Siegmund, Bharat Thyagarajan, Eileen M Crimmins

Abstract read
PubMed Publisher
In one paragraph

Article in npj aging, 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

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Thalida Em ArpawongLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA. arpawong@usc.edu.ORCID http://orcid.org/0000-0001-9671-9535
Steve ColeDavid Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Harshanna BadheshaLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Jung Ki KimLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Christopher R BeamDornsife College of Arts and Sciences, University of Southern California, Los Angeles, CA, USA.
Eric T KlopackSchool of Public Health, Indiana University, Bloomington, IN, USA.
Kimberly SiegmundDivision of Biostatistics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Bharat ThyagarajanDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Eileen M CrimminsLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.

Funding

USC/UCLA Center on Biodemography &Population HealthP30AG017265 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JENNIFER A AILSHIRE · 1999 to 2026
$17.9M
NIA NIH HHS P30 AG017265
6 · The paper itself

Abstract

Epigenetic clocks derived from DNA methylation robustly predict biological aging, health, and mortality, yet differ substantially in their predictive profiles. The biological processes underlying these differences remain poorly understood. Using data from 3227 participants in the U.S. Health and Retirement Study, with contemporaneous DNA methylation and RNA-sequencing, we examined the five most widely used epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE). We conducted differential gene expression analyses to identify clock-specific gene expression levels and enriched biological pathways, to reveal substantial heterogeneity in the molecular processes captured by each clock. We further derived transcriptomic aging gene scores (TAGS) from differentially expressed genes associated with each age acceleration clock, and evaluated their associations with aging-related phenotypes. TAGS complemented DNAm clocks, and in several cases, showed stronger associations with age-related morbidities and mortality. Findings unveiled more unique than common biological processes underlying clocks, illuminating their internal mechanisms, and advancing their interpretability for aging research and clinical applications.

Identifiers

PMID42477337

What OpenQuestion holds

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Registered trials

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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.