A Biophysics of Epigenetic Rejuvenation


Singh P.B.
August 2025Multidisciplinary Digital Publishing Institute (MDPI)

Cells
2025#14Issue 16

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 (Formula presented.) and (Formula presented.). 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.

age reprogramming , eAge , epigenetic rejuvenation , Flory–Huggins parameter , H3K27me3 , H3K9me3 , Hi-C , partial reprogramming , Shannon entropy

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Department of Biomedical Sciences, School of Medicine, Nazarbayev University, 5/1 Kerei, Zhanibek Khandar Street, Astana, 010000, Kazakhstan

Department of Biomedical Sciences

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