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Updated: Jun 26, 2025

Techniques to Induce and Quantify Cellular Senescence

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

Quantifying the stochastic component of epigenetic aging.

Huige Tong¹, Varun B Dwaraka², Qingwen Chen³

¹CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

|May 9, 2024

Summary

Epigenetic clocks

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Area of Science:

Epigenetics
Aging Research
Computational Biology

Background:

DNA methylation (DNAm) clocks estimate chronological and biological age.
The acquisition of age-associated DNAm changes appears quasi-stochastic.
Understanding the stochastic component is crucial for interpreting epigenetic clock accuracy.

Purpose of the Study:

To quantify the proportion of epigenetic clock accuracy attributable to stochastic DNAm changes.
To investigate whether biological aging reflects nonstochastic processes.
To differentiate stochastic from nonstochastic drivers of age acceleration.

Main Methods:

Development of realistic simulation models using DNAm data from sorted immune cells.
Analysis of over 22,770 sorted and whole-blood samples across 25 independent cohorts.
Statistical modeling to assess the contribution of stochastic processes to clock accuracy and age acceleration.

Main Results:

66-75% of Horvath's clock accuracy, 90% of Zhang's clock accuracy, and 63% of PhenoAge clock accuracy can be driven by stochastic processes.
Age acceleration in males (Horvath's clock) and in severe COVID-19 cases/smokers (PhenoAge clock) are driven by nonstochastic processes.
The proportion of stochasticity varies significantly across different epigenetic clocks.

Conclusions:

A substantial portion of epigenetic clock accuracy is explained by stochastic DNAm changes.
Nonstochastic processes are key drivers of biological aging and specific age acceleration phenomena.
These findings refine the interpretation of epigenetic clocks and their relationship to aging.