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August 17, 2025Open Access

A Biophysics of Epigenetic Rejuvenation

PSPrim B. SinghMaharana Pratap University of Agriculture and Technology

Key Points

Epigenetic rejuvenation restores the Flory–Huggins parameter, associated with youthfulness, indicating a reversal of aging effects.
As cells age, epigenetic drift decreases the Flory–Huggins parameter, leading to a smoother epigenetic landscape and increased epigenetic age.
The study uses a novel framework integrating machine learning and polymer physics to explore epigenetics at the molecular level.
Findings emphasize the importance of Shannon entropy in understanding epigenetic aging processes and potential rejuvenation methods.

Abstract

We present a synthesis based on epigenetics, machine learning and polymer physics from which emerges new relationships between the thermodynamic Flory–Huggins parameter (χ), epigenetic age (eAge) and Shannon entropy. Using a framework for the estimation of χ in the nuclear environment we show that χ∝eAge−1 and χ∝Shannon Entropy−1. As cells age, epigenetic drift results in “smoothing out” of the epigenetic landscape reducing the magnitude of χ. Epigenetic rejuvenation reverses epigenetic drift and restores χ to levels found in young cells with concomitant reduction in both eAge and Shannon entropy.

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