Old worms, new tricks: Dynamical instability explains late-life rejuvenation in C. elegans
*Correspondence to:
Collin Y. Ewald, Department of Health Sciences and Technology, ETH Zürich, Zürich 8092, Switzerland.
E-mail: collin-ewald@ethz.ch
Jan Gruber, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore. E-mail: bchjg@nus.edu.sg
Jan Gruber, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore. E-mail: bchjg@nus.edu.sg
Geromedicine. 2027;3:202626. 10.70401/Geromedicine.2026.0044
Received: April 14, 2026Accepted: October 13, 2026Published: October 15, 2026
This article belongs to the Special lssue Understudied Directions in Aging Biology, Quantitative and First-Principles Approaches
This manuscript is made available in its unedited form to allow early access to the
reported findings. Further editing will be completed before final publication. As
such,
the content may include errors, and standard legal disclaimers are applicable.
Abstract
How is it possible to double the lifespan of an organism already close to death? Many biological theories of aging fail to explain this phenomenon. At the Physics of Aging workshop, we used late-life lifespan extension in Caenorhabditis elegans to illustrate how a simple stochastic dynamical-systems model can naturally account for dramatic geriatric interventions. We build on a Langevin-type framework in which aging can occur in stable or unstable dynamical regimes, depending on whether slow, lifespan-determining modes are initially restoring or non-restoring. We argue that C. elegans operates in the unstable regime, a view supported independently by temporal scaling of survival curves, late-life mortality deceleration, and persistent lifespan effects following transient interventions. In the unstable regime, stochastic fluctuations are amplified over time until a failure threshold is reached as a first-passage event. The instability rate α sets the speed of this divergence, while the nonlinear feedback strength g, together with α, sets the failure boundary zmax = α/g. Auxin-induced degradation of DAF-2 in very old animals is interpreted as a late shift in dynamical parameters, and the model naturally accounts for the resulting lifespan extension without requiring reversal of accumulated structural damage. This reconciles persistent senescent pathologies with restored proteostasis and stress resilience, and suggests that altering regulatory instability, rather than reversing damage, can strongly reshape survival trajectories. More broadly, this work illustrates how low-dimensional, physics-inspired stochastic models can capture key features of aging and motivate new collaborations on late-life interventions.
Keywords
Physics of aging, Langevin model, rejuvenation, longevity, daf-2, temperature, proteohomeostasis
References
-
10. Podolskiy D, Molodtcov I, Zenin A, Kogan V, Menshikov LI, Gladyshev VN, et al. Critical dynamics of gene networks is a mechanism behind ageing and Gompertz law. arXiv [Preprint]. 2016.[DOI]
-
11. Fedichev P, Gruber J. A minimal model explains aging regimes and guides intervention strategies. bioRxiv [Preprint]. 2025.[DOI]
-
20. Blagosklonny MV. Cell senescence, rapamycin and hyperfunction theory of aging. Cell Cycle. 2022;21(14):1456-1467.[DOI]
-
30. Alon U. Systems medicine: Physiological circuits and the dynamics of disease. New York: Chapman and Hall/CRC; 2023.[DOI]
-
32. Caenorhabditis Genetics Center, University of Minnesota, Strain RAF2181. Available from: https://cgc. umn.edu/strain/RAF2181
-
36. Stephenson D, Brumfield M, Romero K, Woodcock J, Zineh I, Reiman EM, et al. Alzheimer’s and Parkinson’s diseases face common challenges in therapeutic development: Role of the precompetitive consortium, coalition against major diseases. , J Alzheimers Dis Parkinsonism. 2015;5(1):[DOI]
Copyright
© The Author(s) 2027. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Publisher’s Note
Science Exploration remains a neutral stance on jurisdictional claims in published
maps
and institutional affiliations. The views expressed in this article are solely those
of
the author(s) and do not reflect the opinions of the Editors or the publisher.
Share And Cite
Science Exploration Style
Latumalea D, Molière A, Fedichev P, Ewald CY, Gruber J. Old worms, new tricks: Dynamical instability explains late-life rejuvenation in C. elegans. Geromedicine. 2027;3:202626. https://doi.org/10.70401/Geromedicine.2026.0044
Tips
Copy completed.
Submit a Manuscript
Author Instructions
Cite this Article
Article Metrics
0
View
0
Download
Cited
Article Updates
Get citation
Science Exploration Style
Latumalea D, Molière A, Fedichev P, Ewald CY, Gruber J. Old worms, new tricks: Dynamical instability explains late-life rejuvenation in C. elegans. Geromedicine. 2027;3:202626. https://doi.org/10.70401/Geromedicine.2026.0044
copy
Share Link
copy