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Temperature excursions far from the optimum lead to heat- or cold-shock responses, which have been extensively studied. We hypothesized that, even within a physiological range of temperature whose extremes are not stressful by themselves, the need for constant adjustment to frequent temperature fluctuations might be deleterious. We find that frequent fluctuations between physiological temperatures severely impair the short-term survival of C. elegans in a frequency-dependent manner. We show that the fluctuations impact both the soma and the germline, with the mechanisms that lead to short-term death requiring fertility. Using a survival assay with a candidate gene approach, we identified both hypersensitive and resistant mutants. The nature of the corresponding genes suggests that temperature sensing and mitochondrial function are particularly key to survival under temperature acclimation stress. However, the lack of response from reporter genes designed to reveal classic cellular stresses as well as the molecular identities of the hypersensitive, unaffected, and resistant mutants, suggests that acclimation stress represents a novel type of stress with potentially severely deleterious consequences for animals.<\/jats:p>","DOI":"10.1093\/genetics\/iyag157","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:13:09Z","timestamp":1781849589000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic analysis of sensitivity to temperature fluctuations identifies acclimation stress as a novel type of cellular stress in\n                    <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1093","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8727-9902","authenticated-orcid":false,"given":"Noah","family":"Lilienfeldt","sequence":"first","affiliation":[{"name":"Department of Biology, McGill University , Montreal , H3A 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