Meta-analytic evidence for the anti-aging effect of hormesis on Caenorhabditis elegans

Mild stress-induced hormesis, as a promising strategy to improve longevity and healthy aging, meets both praise and criticism. To comprehensively assess the applicability of hormesis in aging intervention, this meta-analysis was conducted focusing on the effect of hormesis on Caenorhabditis elegans. Twenty-six papers involving 198 effect size estimates met the inclusion criteria. Meta-analytic results indicated that hormesis could significantly extend the mean lifespan of C. elegans by 16.7% and 25.1% under normal and stress culture conditions (p < 0.05), respectively. The healthspan assays showed that hormesis remarkably enhanced the bending frequency and pumping rate of worms by 28.9% and 7.0% (p < 0.05), respectively, while effectively reduced the lipofuscin level by 15.9% (p < 0.05). The obviously increased expression of dauer formation protein-16 (1.66-fold) and its transcriptional targets, including superoxide dismutase-3 (2.46-fold), catalase-1 (2.32-fold) and small heat shock protein-16.2 (2.88-fold) (p < 0.05), was one of the molecular mechanisms underlying these positive effects of hormesis. This meta-analysis provided strong evidence for the anti-aging role of hormesis, highlighting its lifespan-prolonging, healthspan-enhancing and resistance-increasing effects on C. elegans. Given that dauer formation protein-16 was highly conservative, hormesis offered the theoretical possibility of delaying intrinsic aging through exogenous intervention among humans.