{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T02:43:19Z","timestamp":1771900999598,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,20]]},"group-title":"Developmental Biology","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Suspended animation, a state of extreme quiescence with microscopically invisible movement and development, is a remarkable yet poorly understood stress resilience strategy in animals. Here, we describe a newly discovered form of suspended animation inducible by high-population density in isosmotic liquids in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  throughout larval development and adulthood. Transcriptomic, metabolomic and live-cell activity reporter imaging analyses reveal striking molecular and cellular landscape changes 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.\n                <\/jats:p>","DOI":"10.64898\/2026.02.19.706910","type":"posted-content","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T22:40:24Z","timestamp":1771627224000},"source":"Crossref","is-referenced-by-count":0,"title":["Induction and regulation of a reversible form of suspended animation in\n                  <i>C. elegans<\/i>"],"prefix":"10.64898","author":[{"given":"Junqiang","family":"Liu","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingying","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan Leon","family":"Catrow","sequence":"additional","affiliation":[{"name":"Metabolomics Core Research Facility, Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quentinn","family":"Pearce","sequence":"additional","affiliation":[{"name":"Metabolomics Core Research Facility, Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijian","family":"Ji","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Supeng Winnie","family":"Yang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akash","family":"Balakrishnan","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E.","family":"Cox","sequence":"additional","affiliation":[{"name":"Metabolomics Core Research Facility, Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5619-7485","authenticated-orcid":false,"given":"Dengke K.","family":"Ma","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA"},{"name":"Department of Physiology, University of California San Francisco, San Francisco, CA, USA"},{"name":"Innovative Genomics Institute USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026022317501743000_2026.02.19.706910v1.1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.054403"},{"key":"2026022317501743000_2026.02.19.706910v1.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.236.4804.1003"},{"key":"2026022317501743000_2026.02.19.706910v1.3","doi-asserted-by":"crossref","unstructured":"Padilla, P. A. & Roth, M. B. Oxygen deprivation causes suspended animation in the zebrafish embryo. Proc Natl Acad Sci U S A G8 , 7331\u20137335 (2001).","DOI":"10.1073\/pnas.131213198"},{"key":"2026022317501743000_2026.02.19.706910v1.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1089705"},{"key":"2026022317501743000_2026.02.19.706910v1.5","unstructured":"Nystul, M. B. R. and T. Buying Time in Suspended Animation. Scientific American https:\/\/www.scientificamerican.com\/article\/buying-time-in-suspended\/ (2005)."},{"key":"2026022317501743000_2026.02.19.706910v1.6","doi-asserted-by":"crossref","unstructured":"Blackstone, E. , Morrison, M. & Roth, M. B. H2S induces a suspended animation-like state in mice. Science 308, 518 (2005).","DOI":"10.1126\/science.1108581"},{"key":"2026022317501743000_2026.02.19.706910v1.7","doi-asserted-by":"publisher","DOI":"10.4161\/cc.19444"},{"key":"2026022317501743000_2026.02.19.706910v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50111-8"},{"key":"2026022317501743000_2026.02.19.706910v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01325-3"},{"key":"2026022317501743000_2026.02.19.706910v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.04.048"},{"key":"2026022317501743000_2026.02.19.706910v1.11","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s00424-018-2244-7","article-title":"Hibernating astronauts-science or fiction?","volume":"471","year":"2019","journal-title":"Pffugers Arch"},{"key":"2026022317501743000_2026.02.19.706910v1.12","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.01-12-0594"},{"key":"2026022317501743000_2026.02.19.706910v1.13","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E09-09-0787"},{"key":"2026022317501743000_2026.02.19.706910v1.14","doi-asserted-by":"crossref","unstructured":"Hajeri, V. A. , Stewart, A. M. , Moore, L. L. & Padilla, P. A. Genetic analysis of the spindle checkpoint genes san-1, mdf-2, bub-3 and the CENP-F homologues hcp-1 and hcp-2 in Caenorhabditis elegans. Cell Div 3, 6 (2008).","DOI":"10.1186\/1747-1028-3-6"},{"key":"2026022317501743000_2026.02.19.706910v1.15","doi-asserted-by":"crossref","unstructured":"Ghose, P. , Park, E. C. , Tabakin, A. , Salazar-Vasquez, N. & Rongo, C. Anoxia-reoxygenation regulates mitochondrial dynamics through the hypoxia response pathway, SKN-1\/Nrf, and stomatin-like protein STL-1\/SLP-2. PLoS Genet G, e1004063 (2013).","DOI":"10.1371\/journal.pgen.1004063"},{"key":"2026022317501743000_2026.02.19.706910v1.16","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235753"},{"key":"2026022317501743000_2026.02.19.706910v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2010.02.006"},{"key":"2026022317501743000_2026.02.19.706910v1.18","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1701508"},{"key":"2026022317501743000_2026.02.19.706910v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(75)90109-8"},{"key":"2026022317501743000_2026.02.19.706910v1.20","doi-asserted-by":"publisher","DOI":"10.1126\/science.6896933"},{"key":"2026022317501743000_2026.02.19.706910v1.21","first-page":"994","article-title":"The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans","volume":"38G","year":"1997","journal-title":"Nature"},{"key":"2026022317501743000_2026.02.19.706910v1.22","doi-asserted-by":"publisher","DOI":"10.1895\/wormbook.1.155.1"},{"key":"2026022317501743000_2026.02.19.706910v1.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1319"},{"key":"2026022317501743000_2026.02.19.706910v1.24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810338106"},{"key":"2026022317501743000_2026.02.19.706910v1.25","doi-asserted-by":"crossref","first-page":"861686","DOI":"10.3389\/fragi.2022.861686","article-title":"HSF-1: Guardian of the Proteome Through Integration of Longevity Signals to the Proteostatic Network","volume":"3","year":"2022","journal-title":"Front Aging"},{"key":"2026022317501743000_2026.02.19.706910v1.26","doi-asserted-by":"publisher","DOI":"10.1126\/science.1253168"},{"key":"2026022317501743000_2026.02.19.706910v1.27","doi-asserted-by":"crossref","unstructured":"Brunquell, J. , Morris, S. , Lu, Y. , Cheng, F. & Westerheide, S. D. The genome-wide role of HSF-1 in the regulation of gene expression in Caenorhabditis elegans. BMC Genomics 17, (2016).","DOI":"10.1186\/s12864-016-2837-5"},{"key":"2026022317501743000_2026.02.19.706910v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2918"},{"key":"2026022317501743000_2026.02.19.706910v1.29","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.106.069633"},{"key":"2026022317501743000_2026.02.19.706910v1.30","doi-asserted-by":"crossref","unstructured":"Somogyv\u00e1ri, M. , Gecse, E. & S\u0151ti, C. DAF-21\/Hsp90 is required for C. elegans longevity by ensuring DAF-16\/FOXO isoform A function. Sci Rep 8, 12048 (2018).","DOI":"10.1038\/s41598-018-30592-6"},{"key":"2026022317501743000_2026.02.19.706910v1.31","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083701"},{"key":"2026022317501743000_2026.02.19.706910v1.32","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.104.028423"},{"key":"2026022317501743000_2026.02.19.706910v1.33","doi-asserted-by":"crossref","unstructured":"Sun, Y. et al. Lysosome activity is modulated by multiple longevity pathways and is important for lifespan extension in C. elegans. Elife G , e55745 (2020).","DOI":"10.7554\/eLife.55745.sa2"},{"key":"2026022317501743000_2026.02.19.706910v1.34","doi-asserted-by":"crossref","unstructured":"Kumsta, C. , Chang, J. T. , Schmalz, J. & Hansen, M. Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans. Nat Commun 8, 14337 (2017).","DOI":"10.1038\/ncomms14337"},{"key":"2026022317501743000_2026.02.19.706910v1.35","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/s43587-023-00470-6","article-title":"Tubular lysosome induction couples animal starvation to healthy aging","volume":"3","year":"2023","journal-title":"Nat Aging"},{"key":"2026022317501743000_2026.02.19.706910v1.36","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/s41586-024-07249-8","article-title":"The HEAT repeat protein HPO-27 is a lysosome fission factor","volume":"628","year":"2024","journal-title":"Nature"},{"key":"2026022317501743000_2026.02.19.706910v1.37","doi-asserted-by":"crossref","unstructured":"Cook, A. S. I. et al. Structural pathway for PI3-kinase regulation by VPS15 in autophagy. Science 388, eadl3787 (2025).","DOI":"10.1126\/science.adl3787"},{"key":"2026022317501743000_2026.02.19.706910v1.38","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1182\/blood.2020006871","article-title":"Mammalian VPS45 orchestrates trafficking through the endosomal system","volume":"137","year":"2021","journal-title":"Blood"},{"key":"2026022317501743000_2026.02.19.706910v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3013"},{"key":"2026022317501743000_2026.02.19.706910v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2023.10.006"},{"key":"2026022317501743000_2026.02.19.706910v1.41","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202402918"},{"key":"2026022317501743000_2026.02.19.706910v1.42","doi-asserted-by":"crossref","unstructured":"Ferkey, D. M. , Sengupta, P. & L\u2019Etoile, N. D. Chemosensory signal transduction in Caenorhabditis elegans. Genetics 217, iyab004 (2021).","DOI":"10.1093\/genetics\/iyab004"},{"key":"2026022317501743000_2026.02.19.706910v1.43","doi-asserted-by":"crossref","unstructured":"Trojanowski, N. F. & Raizen, D. M. Call it Worm Sleep. Trends Neurosci 3G , 54\u201362 (2016).","DOI":"10.1016\/j.tins.2015.12.005"},{"key":"2026022317501743000_2026.02.19.706910v1.44","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.117.300521"},{"key":"2026022317501743000_2026.02.19.706910v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2016.07.048"},{"key":"2026022317501743000_2026.02.19.706910v1.46","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.118.300241"},{"key":"2026022317501743000_2026.02.19.706910v1.47","doi-asserted-by":"crossref","unstructured":"Watteyne, J. , Chudinova, A. , Ripoll-S\u00e1nchez, L. , Schafer, W. R. & Beets, I. Neuropeptide signaling network of Caenorhabditis elegans: from structure to behavior. Genetics 228, iyae141 (2024).","DOI":"10.1093\/genetics\/iyae141"},{"key":"2026022317501743000_2026.02.19.706910v1.48","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709060200"},{"key":"2026022317501743000_2026.02.19.706910v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.05.001"},{"key":"2026022317501743000_2026.02.19.706910v1.50","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.116.192898"},{"key":"2026022317501743000_2026.02.19.706910v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.08.001"},{"key":"2026022317501743000_2026.02.19.706910v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.06.023"},{"key":"2026022317501743000_2026.02.19.706910v1.53","doi-asserted-by":"crossref","unstructured":"Ghaddar, A. et al. Whole-body gene expression atlas of an adult metazoan. Sci Adv G , ead g0506 (2023).","DOI":"10.1101\/2022.11.06.515345"},{"key":"2026022317501743000_2026.02.19.706910v1.54","doi-asserted-by":"crossref","unstructured":"Packer, J. S. et al. A lineage-resolved molecular atlas of C. elegans embryogenesis at single-cell resolution. Science 365, eaax1971 (2019).","DOI":"10.1126\/science.aax1971"},{"key":"2026022317501743000_2026.02.19.706910v1.55","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.119.302293"},{"key":"2026022317501743000_2026.02.19.706910v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08132-2"},{"key":"2026022317501743000_2026.02.19.706910v1.57","first-page":"533.83","article-title":"Measuring the cAMP\/PKA signaling pathway in stress-induced sleep using C. elegans as a model organism","volume":"32","year":"2018","journal-title":"The FASEB Journal"},{"key":"2026022317501743000_2026.02.19.706910v1.58","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318239355d"},{"key":"2026022317501743000_2026.02.19.706910v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2014.11.001"},{"key":"2026022317501743000_2026.02.19.706910v1.60","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez-P\u00e9rez, P. et al. miR-1 sustains muscle physiology by controlling V-ATPase complex assembly. Sci Adv 7, eabh1434 (2021).","DOI":"10.1126\/sciadv.abh1434"},{"key":"2026022317501743000_2026.02.19.706910v1.61","doi-asserted-by":"crossref","unstructured":"Cm, W. & Bl, B. \u01eauorum sensing: cell-to-cell communication in bacteria. Annual review of cell and developmental biology 21, (2005).","DOI":"10.1146\/annurev.cellbio.21.012704.131001"},{"key":"2026022317501743000_2026.02.19.706910v1.62","unstructured":"M, de B . & Ci, B. Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans. Cell G4 , (1998)."},{"key":"2026022317501743000_2026.02.19.706910v1.63","doi-asserted-by":"crossref","unstructured":"Ds, P . Social and sexual behaviors in C. elegans: the first fifty years. Journal of neurogenetics 34, (2020).","DOI":"10.1080\/01677063.2020.1838512"},{"key":"2026022317501743000_2026.02.19.706910v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.07.007"},{"key":"2026022317501743000_2026.02.19.706910v1.65","doi-asserted-by":"crossref","unstructured":"Savini, M. , Zhao, \u01ea. & Wang, M. C. Lysosomes: Signaling Hubs for Metabolic Sensing and Longevity. Trends Cell Biol 2G , 876\u2013887 (2019).","DOI":"10.1016\/j.tcb.2019.08.008"},{"key":"2026022317501743000_2026.02.19.706910v1.66","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.tcb.2022.10.004","article-title":"Macroautophagy in quiescent and senescent cells: a pathway to longevity?","volume":"33","year":"2023","journal-title":"Trends Cell Biol"},{"key":"2026022317501743000_2026.02.19.706910v1.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2387-5"},{"key":"2026022317501743000_2026.02.19.706910v1.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2009.09.005"},{"key":"2026022317501743000_2026.02.19.706910v1.69","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2163-6"},{"key":"2026022317501743000_2026.02.19.706910v1.70","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/20031967725"},{"key":"2026022317501743000_2026.02.19.706910v1.71","doi-asserted-by":"crossref","unstructured":"Davis, M. W. et al. Rapid single nucleotide polymorphism mapping in C. elegans. BMC Genomics 6, 118 (2005).","DOI":"10.1186\/1471-2164-6-118"},{"key":"2026022317501743000_2026.02.19.706910v1.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.04.026"},{"key":"2026022317501743000_2026.02.19.706910v1.73","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.12.037"},{"key":"2026022317501743000_2026.02.19.706910v1.74","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-2023(03)00050-1"},{"key":"2026022317501743000_2026.02.19.706910v1.75","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb04966.x"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.02.19.706910","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T01:50:32Z","timestamp":1771897832000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.02.19.706910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":75,"URL":"https:\/\/doi.org\/10.64898\/2026.02.19.706910","relation":{},"subject":[],"published":{"date-parts":[[2026,2,20]]},"subtype":"preprint"}}