Abstract
Suspended animation, a state of profound metabolic, behavioral and developmental quiescence, is a remarkable yet poorly understood stress resilience strategy in animals. Here, we describe a previously uncharacterized form of suspended animation inducible by high-population density in isosmotic liquids in C. elegans throughout larval development and adulthood. Transcriptomic, metabolomic, and live-cell activity reporter imaging analyses reveal striking molecular and cellular landscape changes caused by such liquid-induced suspended animation (LISA), including remodeling of gene expression programs, energy metabolites, lysosomal and mitochondrial morphology. Genetic screens identify mutants with altered stress responses and survival against LISA. While key endo-lysosomal regulators promote survival during LISA, organelle remodeling and a neuronal axis via downstream neuropeptide and cAMP/PKA signaling orchestrate behavioral awakening from LISA. Our findings define a facile paradigm for reversible SA, providing a powerful model system to uncover key molecular and cellular mechanisms governing an extreme case of reversible life arrest and dormancy.
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Data availability
RNA-seq data have been deposited in the Gene Expression Omnibus under accession number GSE320035. All other data supporting the findings of this study, as well as reagents generated and/or analyzed during the current study, are provided and available from the corresponding author upon reasonable request. Source data are provided with this paper.
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Acknowledgements
Some strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440), and by Drs. Peter Douglas, Henrik Bringmann, Daniel Colón-Ramos, Noelle L’Etoile, Rosa E. Navarro González, Josh Kaplan, Matt Nelson, and Xiaochen Wang. We also thank the C. elegans Reverse Genetics Core Facility (University of British Columbia), National Bioresource Project (Tokyo Women’s Medical University), Wormbase.org (NIH grant #U24 HG002223 to P. Sternberg), Wormatlas.org (NIH grant #OD010943 to D.H. Hall.), wormseq.org (Dr. E. O’Rourke), Aging Atlas (Dr. M. Wang) and CenGen for invaluable resources. The work was supported by NIH grants (R35GM139618 to D.K.M.), AHA (24TPA1288391) and 2025 UCSF PBBR New Frontier Research Award (D.K.M.).
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J.L. designed, performed and analyzed most experiments in this work, including characterization of LISA properties, live reporter imaging and LISA phenotypic assays. B.W. made the initial observations on LISA and stress reporter expression and performed EMS screens and genetic mutant mapping. Z.J. and S.W.Y. helped with WGS and imaging analyses. A.B. assisted with data analysis. J.E.C. and J.L.C. performed and analyzed LC-MS and GC-MS experiments. D.K.M. designed and analyzed the C. elegans experiments, contributed to project conceptualization, funding acquisition and editing the manuscript. All authors contributed to research materials, project conceptualization and editing manuscript.
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Liu, J., Wang, B., Leon Catrow, J. et al. Induction and regulation of reversible suspended animation in C. elegans. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71247-9
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DOI: https://doi.org/10.1038/s41467-026-71247-9
