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bioRxiv · 10.1101/2023.07.25.550452

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

Jiang, W. I.·Belly, H. D.·Wang, B. K.·Wong, A.·Kim, M.·Oh, F.·DeGeorge, J.·Huang, X.·Guang, S.·Weiner, O. K.·Ma, D. K.
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Abstract

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 marked 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. TeaserStudies reveal mechanisms of how early-life heat exposure produces long-lasting benefits on longevity in the nematode C. elegans.

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Jiang, W. I., Belly, H. D., Wang, B. K., Wong, A., Kim, M., Oh, F., DeGeorge, J., Huang, X., Guang, S., Weiner, O. K., Ma, D. K.. 2023-07-25. Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin. https://doi.org/10.1101/2023.07.25.550452

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