Berlin 2024 – scientific programme
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BP: Fachverband Biologische Physik
BP 29: Statistical Physics of Biological Systems II (joint session BP/DY)
BP 29.7: Talk
Thursday, March 21, 2024, 11:15–11:30, H 1028
Geometry and epigenetic memory during ageing — •Matteo Ciarchi1, Benjamin D. Simons3, and Steffen Rulands2 — 1Max Planck Institute for the Physics of Complex Systems, Dresden — 2Ludwig-Maximilians-Universität, München — 3Department of Applied Mathematics and Theoretical Physics, Cambridge
Ageing is the decline of the physiological function of an organism over time. This process has been shown to be tightly correlated to changes in epigenetic modifications of the DNA. But how does the slow process of ageing over decades emerge from the fast molecular changes in the epigenome? Here, we show that the interplay between fluctuations and DNA geometry gives rise to memory that translates short-term molecular changes to a slow drift on the time-scales of aging. We draw on sequencing experiments that compare DNA methylation on the time scales of few cell divisions to longitudinal measurements over the much longer time scales of aging. We find that the drift of DNA methylation over time in both cases is highly nonlinear and cannot be explained by known biochemical processes. In order to understand these observations, we derive a field-theoretic framework that couples epigenetic processes along the DNA sequence with dynamic geometrical changes of the DNA in three-dimensional space. Using this theory, we show that the conformational changes in three-dimensional space allow for memory to form along the DNA sequence. Taken together, our work shows that epigenetic ageing is the accumulation of fast, intrinsic molecular processes over long time scales.
Keywords: Epigenetics; Ageing; Polymers; Memory