Lexicon
Horvath Clock
Also known as Horvath epigenetic clock
Definition
In 2013, a multi-tissue age estimator using the DNA methylation pattern of 353 CpGs was developed by Steve Horvath, and this estimator was named the epigenetic clock. [1] The Horvath clock is a first-generation model, in contrast to advanced second- and third-generation clocks such as DNA GrimAge and DunedinPACE. [2]
How it works
The estimated age produced by the epigenetic clock is named DNAmAge and can serve as a biomarker of aging predicting the risk of age-associated diseases and mortality. [1] Unlike telomere-based and transcriptomic aging clocks, the Horvath DNA methylation clock provides the most accurate determination of biological age relative to chronological age, yet it correlates poorly with those other clock types. [3]
Connected concepts
How it's measured
The clock is computed from genome-wide DNA methylation data, and because it is a multi-tissue estimator it applies across a range of tissue types rather than blood alone. [1] An improved version using the DNA methylation pattern of 391 CpGs was developed in 2018. [1]
What levels mean
Horvath age acceleration, the residual of DNAmAge against chronological age, is used to assess whether an individual is aging faster or slower than expected and has been applied to conditions ranging from post-traumatic stress disorder to cancer risk. [4] [5] Higher physical activity is significantly associated with lower biological age as measured by Horvath epigenetic age acceleration, though the evidence is predominantly cross-sectional. [6]
Community knowledge
## Historical Context
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- 1.Matsuyama M, Søraas A, Yu S, Kim K, Stavrou EX, Caimi PF, Wald D, deLima M. Analysis of epigenetic aging in vivo and in vitro: Factors controlling the speed and direction. Exp Biol Med (Maywood) · 2020
- 2.Evangelina R, Ganesan S, George M. The Epigenetic Landscape: From Molecular Mechanisms to Biological Aging. Rejuvenation Res · 2025
- 3.Mendelsohn AR, Larrick JW. Telomerase May Paradoxically Accelerate Aging of the DNA Methylome. Rejuvenation Res · 2018
- 4.Zhao X, Katrinli S, McCormick BM, Miller MW, Nugent NR, Wani AH, Zannas AS, Aiello AE. PTSD and epigenetic aging: a longitudinal meta-analysis. Psychol Med · 2025
- 5.McLennan E, Li DL, Southey MC, Dugué PA. Epigenetic Ageing and Breast Cancer Risk: A Systematic Review. Cancer Med · 2024
- 6.Shan J, Tay JH, Wang W, Tan R, Joshi R, Maier AB, Feng L.
Community discussion
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