Statistical Physics Approaches to DNA Methylation and Aging (Steffen Rulands)

In this episode of the Epigenetics Podcast, we talked with Steffen Rulands from the Ludwig Maximilian University of Munich about how methods from statistical physics can be used to study collective phenomena in biology. We discuss his path from physics into stem cell biology and epigenetics, and how this background shapes the questions he asks in his work.

We talk about his lab’s focus on quantitative and mechanistic modeling rather than wet lab experiments. He explains that he uses single-cell genomics and other datasets to understand how cells make decisions, with interests ranging from development and regeneration to aging and rejuvenation.

A major topic is DNA methylation during embryonic development. We discuss how he and his collaborators found surprisingly simple, self-similar patterns in methylation over time and along the genome, and how they explained these patterns with a feedback loop between chromatin conformation and methylation deposition.

We also cover his collaboration on social insect colonies, where he examines how DNA methylation and gene regulation help explain stable social roles and flexibility when the queen is removed. In that system, interactions across the whole nest shape the regulation of queen- and worker-associated genes.

Later in the conversation, we turn to aging. We discuss his recent work on temporal hierarchies in epigenetic aging and on collective dynamics of DNA methylation, where we ask how molecular-scale events can combine to produce the long timescale of organismal aging. We close by talking about rejuvenation, general principles in aging, and the role of physics in identifying what is generic versus what is specifically regulated in biology.

References

• Rulands, S., Lee, H. J., Clark, S. J., Angermueller, C., Smallwood, S. A., Krueger, F., Mohammed, H., Dean, W., Nichols, J., Rugg-Gunn, P., Kelsey, G., Stegle, O., Simons, B. D., & Reik, W. (2018). Genome-Scale Oscillations in DNA Methylation during Exit from Pluripotency. Cell systems, 7(1), 63–76.e12. https://doi.org/10.1016/j.cels.2018.06.012
• Olmeda, F., Lohoff, T., Kafetzopoulos, I. et al. Scaling and self-similarity in the formation of the embryonic epigenome. Nat. Phys. 22, 931–940 (2026). https://doi.org/10.1038/s41567-026-03263-x

Related Episodes

• Biophysical Modeling of 3-D Genome Organization (Leonid Mirny)
• The Interplay of Nutrition, Metabolic Pathways, and Epigenetic Regulation (Ferdinand von Meyenn)
• Epigenetic Reprogramming During Mammalian Development (Wolf Reik)

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