Aging | DNA Methylation GrimAge Version 2


“[…] GrimAge2 complements existing clinical biomarkers when evaluating an individual’s aging rate.”

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BUFFALO, NY- December 21, 2022 – A new research paper was published in Aging (listed as “Aging (Albany NY)” by MEDLINE/PubMed and “Aging-US” by Web of Science) Volume 14, Issue 23, entitled, “DNA methylation GrimAge version 2.”

Researchers Ake T. Lu, Alexandra M. Binder, Joshua Zhang, Qi Yan, Alex P. Reiner, Simon R. Cox, Janie Corley, Sarah E. Harris, Pei-Lun Kuo, Ann Z. Moore, Stefania Bandinelli, James D. Stewart, Cuicui Wang, Elissa J. Hamlat, Elissa S. Epel, Joel D. Schwartz, Eric A. Whitsel, Adolfo Correa, Luigi Ferrucci, Riccardo E. Marioni, and Steve Horvath from the University of California Los Angeles, Altos Labs, University of Hawaii at Manoa, Fred Hutchinson Cancer Research Center, University of Edinburgh, National Institute on Aging, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Harvard T.H. Chan School of Public Health, University of California – San Francisco, and the University of Mississippi Medical Center previously described a DNA methylation (DNAm) based biomarker of human mortality risk DNAm GrimAge. In their current study, the researchers describe version 2 of GrimAge (trained on individuals aged between 40 and 92) which leverages two new DNAm based estimators of (log transformed) plasma proteins: high sensitivity C-reactive protein (logCRP) and hemoglobin A1C (logA1C).

“To arrive at version 2 of GrimAge, we developed two additional DNAm based surrogates for plasma proteins that are widely used in the clinic (DNAm logCRP and DNAm logA1C).”

The team evaluated GrimAge2 in 13,399 blood samples across nine study cohorts. After adjustment for age and sex, GrimAge2 outperforms GrimAge in predicting mortality across multiple racial/ethnic groups (meta P=3.6×10-167 versus P=2.6×10-144) and in terms of associations with age related conditions such as coronary heart disease, lung function measurement FEV1 (correlation= -0.31, P=1.1×10-136), computed tomography based measurements of fatty liver disease. The researchers presented evidence that GrimAge version 2 also applies to younger individuals and to saliva samples where it tracks markers of metabolic syndrome. 

DNAm logCRP is positively correlated with morbidity count (P=1.3×10-54). DNAm logA1C is highly associated with type 2 diabetes (P=5.8×10-155). DNAm PAI-1 outperforms the other age-adjusted DNAm biomarkers including GrimAge2 in correlating with triglyceride (cor=0.34, P=9.6×10-267) and visceral fat (cor=0.41, P=4.7×10-41). Overall, the team demonstrated that GrimAge version 2 is an attractive epigenetic biomarker of human mortality and morbidity risk.

“GrimAge2 will not replace existing clinical biomarkers. Rather, GrimAge2 complements existing clinical biomarkers when evaluating an individual’s aging rate.”


Corresponding Author: Steve Horvath

Corresponding Email: [email protected] 

Keywords: DNA methylation, epigenetic clock, mortality, healthspan

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About Aging-US:

Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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