GrimAge Outperforms Other Epigenetic Clocks in the Prediction of Age-Related Clinical Phenotypes and All-Cause Mortality
Open accessAbstract
The aging process is characterized by the presence of high interindividual variation between individuals of the same chronical age prompting a search for biomarkers that capture this heterogeneity. Epigenetic clocks measure changes in DNA methylation levels at specific CpG sites that are highly correlated with calendar age. The discrepancy resulting from the regression of DNA methylation age on calendar age is hypothesized to represent a measure of biological aging with a positive/negative residual signifying age acceleration (AA)/deceleration, respectively. The present study examines the associations of 4 epigenetic clocks—Horvath, Hannum, PhenoAge, GrimAge—with a wide range of clinical phenotypes (walking speed, grip strength, Fried frailty, polypharmacy, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), Sustained Attention Reaction Time, 2-choice reaction time), and with all-cause mortality at up to 10-year follow-up, in a sample of 490 participants in the Irish Longitudinal Study on Ageing (TILDA). HorvathAA and HannumAA were not predictive of health; PhenoAgeAA was associated with 4/9 outcomes (walking speed, frailty MOCA, MMSE) in minimally adjusted models, but not when adjusted for other social and lifestyle factors. GrimAgeAA by contrast was associated with 8/9 outcomes (all except grip strength) in minimally adjusted models, and remained a significant predictor of walking speed, .polypharmacy, frailty, and mortality in fully adjusted models. Results indicate that the GrimAge clock represents a step-improvement in the predictive utility of the epigenetic clocks for identifying age-related decline in an array of clinical phenotypes promising to advance precision medicine.
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The DNAm GrimAge clock shows consistently stronger associations with various measures of age-related dysfunction, including heart disease, frailty, and cognitive and physical decline, compared to other clocks.
“The DNAm GrimAge clock shows consistently stronger associations with various measures of age-related dysfunction, including heart disease, frailty, and cognitive and physical decline, compared to other clocks47,48,50,64–72.”
From Measuring biological age using omics data (2022) · cites this paper as [68]
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- Authors
- McCrory, C., Fiorito, G., Hernandez, B., Polidoro, S., O’Halloran, A. M., Hever, A., Ni Cheallaigh, C., Lu, A. T., Horvath, S., Vineis, P., & Kenny, R. A.
- Affiliations
- Trinity College Dublin (IE)
- University of Sassari (IT)
- Department of Medical Gerontology, Trinity College Dublin, Ireland
- Italian institute for Genomic Medicine (IT)
- Department of Clinical Medicine, St. James Hospital, Dublin, Ireland
- University of California, Los Angeles (US)
- MRC Centre for Environment and Health (GB)
- Corresponding author
- McCrory, Cathal
- ORCID
- Venue
- The Journals of Gerontology: Series A
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-11-19
- Volume
- 76
- Issue
- 5
- Pages
- 741-749
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC8087266
- OpenAlex
- W3106296722
- Cited by
- 464
- References
- 44
- Citations by year
- 2026: 69 · 2025: 116 · 2024: 84 · 2023: 90 · 2022: 72 · 2021: 33
- FWCI
- 15.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- Health Research Board (HRB) of Ireland (EIA-2017-012)
- LIFEPATH (633666)
- Irish Government
- Atlantic Philanthropies
- Irish Life plc
- NIH
- NIA (IU01AG060908)
- 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
- GrimAge, epigenetic clocks, DNA methylation age, accelerated aging, biological aging, all-cause mortality, frailty, walking speed, polypharmacy, cognitive decline, Horvath clock, Hannum clock, PhenoAge clock, TILDA, aging biomarkers
- MeSH terms
- Walking Speed, Frailty, Aging, Female, Genetic Markers, Humans, Longitudinal Studies, Male, Middle Aged, Mortality, Neuropsychological Tests, Phenotype, Hand Strength, DNA Methylation, Polypharmacy, Epigenesis, Genetic
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