Mitochondrial clearance and increased HSF-1 activity are coupled to promote longevity in fasted Caenorhabditis elegans

Autor: Nikolaos Tataridas-Pallas, Yahyah Aman, Rhianna Williams, Hannah Chapman, Kevin J.H. Cheng, Casandra Gomez-Paredes, Gillian P. Bates, John Labbadia
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 6, Pp 109834- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.109834
Popis: Summary: Fasting has emerged as a potent means of preserving tissue function with age in multiple model organisms. However, our understanding of the relationship between food removal and long-term health is incomplete. Here, we demonstrate that in the nematode worm Caenorhabditis elegans, a single period of early-life fasting is sufficient to selectively enhance HSF-1 activity, maintain proteostasis capacity and promote longevity without compromising fecundity. These effects persist even when food is returned, and are dependent on the mitochondrial sirtuin, SIR-2.2 and the H3K27me3 demethylase, JMJD-3.1. We find that increased HSF-1 activity upon fasting is associated with elevated SIR-2.2 levels, decreased mitochondrial copy number and reduced H3K27me3 levels at the promoters of HSF-1 target genes. Furthermore, consistent with our findings in worms, HSF-1 activity is also enhanced in muscle tissue from fasted mice, suggesting that the potentiation of HSF-1 is a conserved response to food withdrawal.
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