Abstract
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.
Highlights
Hormesis, a biphasic dose-response characterized by low-dose stimulation and high-dose inhibition, is considered as a significant toxicological concept to account for the beneficial effects of mild stress [1, 2]
This meta-analysis indicated that hormetic effect could significantly extend the mean lifespan of wild-type worms, with an increase of 16.7% (Random-effect model; standardized mean difference (SMD) = 1.24, 95% confidence intervals (CIs) = 0.77, 1.70; p < 0.05) (Figures 1A and 2) under normal culture condition and 25.1% (Random-effect model; SMD = 1.94, 95% CIs = 0.93, 2.96; p < 0.05) (Figures 1E and 6) under stress culture condition
The lifespan-prolonging, healthspan-enhancing and resistance-increasing effects of hormesis were identified in C. elegans
Summary
A biphasic dose-response characterized by low-dose stimulation and high-dose inhibition, is considered as a significant toxicological concept to account for the beneficial effects of mild stress [1, 2]. As a beneficial compensatory response triggered by mild stress, hormetic individuals generally exhibit better performance than the untreated controls, and the potential anti-aging effect of hormesis has attracted more attention [4, 5]. There are still considerable debates regarding the origin and mechanisms of aging and hormesis, such as the conflicting evidence related to the role of ROS in aging [7, 8], and the hormetic effect manifested by stresswww.aging-us.com induced cost-free benefits or trade-offers with other fitness traits [9, 10]. The anti-aging effect of hormesis remains controversial [4]
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