A Biophysics of Epigenetic Rejuvenation.

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.