Lexicon
PhenoAge
Also known as DNAm PhenoAge
Definition
DNA PhenoAge is one of the most classic epigenetic clocks, developed alongside Horvath's clock, Hannum's clock, and DNA GrimAge as a DNA methylation-based measure of biological age. [1] It is one of the widely used epigenetic clocks, evaluated together with Horvath, GrimAge, and DunedinPACE for predicting mortality, cognitive decline, and cardiovascular outcomes. [2]
How it works
Phenotypic age is a biological age estimate that draws on multi-system clinical biomarkers, and DNA methylation PhenoAge translates this phenotype into a methylation-based clock. [3] As DNA methylation-based age clocks evolved from chronological age estimators into indicators of lifespan and healthspan, estimated epigenetic age acceleration such as PhenoAge acceleration became a predictor of clinical conditions. [4]
Connected concepts
How it's measured
PhenoAge is computed from DNA methylation data, and its output is expressed as PhenoAge acceleration, the residual against chronological age. [5] [6] In a worldwide analysis of epigenetic age acceleration, the PhenoAge model tended to systematically underestimate the age prediction of healthy subjects. [7]
What levels mean
Phenotypic age advancement, calculated as the difference between phenotypic age and chronological age, is treated as an indicator of accelerated biological aging when the residual is positive. [8] Higher PhenoAge epigenetic age acceleration is significantly associated with higher frailty in cross-sectional meta-analysis, with a standardized effect of 0.07. [5] In schizophrenia, PhenoAge showed a significant accelerating effect relative to controls when analyzed apart from Horvath's chronological-age clock. [9]
Community knowledge
## Second-Generation Clocks
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- 1.Duan R, Fu Q, Sun Y, Li Q. Epigenetic clock: A promising biomarker and practical tool in aging. Ageing Res Rev · 2022
- 2.Yamada H. Epigenetic Clocks and EpiScore for Preventive Medicine: Risk Stratification and Intervention Models for Age-Related Diseases. J Clin Med · 2025
- 3.Lu WH. Effect of Modifiable Lifestyle Factors on Biological Aging. JAR Life · 2024
- 4.Noroozi R, Ghafouri-Fard S, Pisarek A, Rudnicka J, Spólnicka M, Branicki W, Taheri M, Pośpiech E. DNA methylation-based age clocks: From age prediction to age reversion. Ageing Res Rev · 2021
- 5.Tay JH, Barros D, Wang W, Wazny VK, Maier AB. Biological age measured by DNA methylation clocks and frailty: a systematic review and meta-analysis. Lancet Healthy Longev · 2025
- 6.Pan Y, Sun X, Huang Z, Zhang R, Li C, Anderson AH, Lash JP, Kelly TN.
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