Tataridas-Pallas, Nikolaos;
Aman, Yahyah;
Williams, Rhianna;
Chapman, Hannah;
Cheng, Kevin JH;
Gomez-Paredes, Casandra;
Bates, Gillian P;
(2024)
Mitochondrial clearance and increased HSF-1 activity are coupled to promote longevity in fasted Caenorhabditis elegans.
iScience
, 27
(6)
, Article 109834. 10.1016/j.isci.2024.109834.
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Mitochondrial clearance and increased HSF-1 activity are coupled to promote longevity in fasted <i>Caenorhabditis eleg.pdf - Accepted Version Download (5MB) | Preview |
Abstract
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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