Molecular insights into diverse heat hormesis regimens in Caenorhabditis elegans

Abstract Heat hormesis describes a biphasic, dose-dependent response in which low levels of heat stress induce beneficial effects, such as enhanced lifespan and stress resilience. This phenomenon is commonly studied in Caenorhabditis elegans using regimens that involve mild heat stress priming, followed by a recovery period and subsequent stress challenge or lifespan measurement. The concept is conserved across species and has gained renewed interest due to its potential relevance to therapeutic strategies, including sauna-based wellness practices. This review synthesizes phenotypic and molecular findings from C. elegans heat hormesis studies, organizing them by regimen type, defined by temperature, duration, and developmental stage of priming. This structure enables comparisons across regimens, revealing both shared and distinct physiological outcomes and mechanistic responses. We highlight current knowledge gaps and discuss considerations for future experimental design, including more consistent control of key variables, to support efforts in identifying optimized conditions with potential translational relevance for health and therapeutic applications. Lastly, we draw from heat hormesis studies performed in mammals to compare methodologies and emphasize conserved mechanisms.