Dynamical Regimes in Rejuvenation
- 1Ludwig-Maximilians-Universitaet Muenchen
Abstract
Biological aging is accompanied by systematic changes in epigenetic modifications and chromatin organization. The reversal of the effects of aging, rejuvenation, is experimentally achieved by the transient induction of factors that modify these marks in cells and organisms. Here, we show that key features of rejuvenation experiments emerge from the biophysical interplay between dynamic epigenetic marks and the three-dimensional conformation of chromatin. Using a minimal field theory and molecular dynamics simulations, we show that the system responds in three distinct temporal regimes. The intermediary regime fulfills necessary conditions for successful rejuvenation. In this regime, the system spends time near a separatrix, allowing for high epigenetic plasticity, while memory retained in the chromatin conformation enables restoration of the original epigenetic correlations. Analysis of sequencing data further supports the predicted coupling between chromatin compaction and epigenetic correlations. Our results provide a physical explanation for how rejuvenation may remodel age-associated epigenetic states without irreversibly erasing cellular identity. We identify a general mechanism by which memory stored in a slow structural variable permits reversible remodeling of a faster internal state.
Related
- Dynamical regimes of excitable cells under pulsed electric fields: From excitation to electroporation
- Skin aging: mechanisms, evaluation, and rejuvenation
- Quantitative Phenotyping of Ion Fluxes in Tip-Growing Cells Under Varying Growth Regimes: A Data Analysis Protocol
- Water as an Active Medium: Distinct Structural-Dynamic Regimes Revealed by Trace Perturbations
- Ablating Design Choices for Protein Ensemble Generators Across Structural Regimes
BibTeX
@misc{rulands2026dynamical,
title = {{Dynamical Regimes in Rejuvenation}},
author = {S. Rulands and M. Ciarchi},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.27.747604},
url = {https://www.biorxiv.org/content/10.64898/2026.08.27.747604v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Dynamical Regimes in Rejuvenation
AU - S. Rulands
AU - M. Ciarchi
PY - 2026
DA - 2026/08/27
PB - bioRxiv
DO - 10.64898/2026.08.27.747604
UR - https://www.biorxiv.org/content/10.64898/2026.08.27.747604v1
AB - Biological aging is accompanied by systematic changes in epigenetic modifications and chromatin organization. The reversal of the effects of aging, rejuvenation, is experimentally achieved by the transient induction of factors that modify these marks in cells and organisms. Here, we show that key features of rejuvenation experiments emerge from the biophysical interplay between dynamic epigenetic marks and the three-dimensional conformation of chromatin. Using a minimal field theory and molecular dynamics simulations, we show that the system responds in three distinct temporal regimes. The intermediary regime fulfills necessary conditions for successful rejuvenation. In this regime, the system spends time near a separatrix, allowing for high epigenetic plasticity, while memory retained in the chromatin conformation enables restoration of the original epigenetic correlations. Analysis of sequencing data further supports the predicted coupling between chromatin compaction and epigenetic correlations. Our results provide a physical explanation for how rejuvenation may remodel age-associated epigenetic states without irreversibly erasing cellular identity. We identify a general mechanism by which memory stored in a slow structural variable permits reversible remodeling of a faster internal state.
ER -