Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin

Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here we show that early-life thermal stress strongly up-regulates tsp-1, a gene encoding the conserved transmembrane tetr...

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Published inbioRxiv : the preprint server for biology
Main Authors Jiang, Wei I, Belly, Henry De, Wang, Bingying K, Wong, Andrew, Kim, Minseo, Oh, Fiona, DeGeorge, Jason, Huang, Xinya, Guang, Shouhong, Weiner, Orion K, Ma, Dengke K
Format Journal Article
LanguageEnglish
Published United States 17.12.2023
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Summary:Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here we show that early-life thermal stress strongly up-regulates tsp-1, a gene encoding the conserved transmembrane tetraspanin in C. elegans. TSP-1 forms prominent multimers and stable web-like structures critical for membrane barrier functions in adults and during aging. The up-regulation of TSP-1 persists even after transient early-life stress. Such regulation requires CBP-1, a histone acetyl-transferase that facilitates initial tsp-1 transcription. Tetraspanin webs form regular membrane structures and mediate resilience-promoting effects of early-life thermal stress. Gain-of-function TSP-1 confers striking C. elegans longevity extension and thermal resilience in human cells. Together, our results reveal a cellular mechanism by which early-life thermal stress produces long-lasting memory-like impact on organismal resilience and longevity.