A Survey of the Evidence for Hormesis to Slow Aging in Nematode Worms
Hormesis is the name given to the process by which lesser degrees of cellular stress and damage can result in long-term benefits to health. Cells react to molecular damage with greater repair and maintenance activities, and when that damage occurs transiently and minimally, the additional efforts to maintain function outweigh any detrimental effects. This can slow aging and extend life in a range of short-lived species. Hormesis depends on complex biochemistry, however, and similar approaches to triggering it can easily fall on the wrong side of the line, causing too much damage, or not enough of a maintenance response. Researchers here review the literature in search of a consensus in the matter of hormesis and aging in the widely studied nematode species C. elegans.
The concept of hormesis arouses great interest, because it is a near-universal and reproducible phenomenon. 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. It seems promising to apply hormesis in aging intervention, which is evidenced by multiple studies, like the beneficial effects of moderate exercise-induced hormesis on body function and aging-related diseases. However, there are still considerable debates regarding the origin and mechanisms of aging and hormesis, such as the conflicting evidence related to the role of reactive oxygen species (ROS) in aging.
At present, most researchers take a wait-and-see attitude to hormetic treatment for human health, due to the contradictory evidence. Thus it is meaningful to conduct a systematic assessment on the existed evidences in the absence of large-scale empirical research on the correlation between hormesis and aging/anti-aging. Meta-analysis is a powerful tool to synthesize multiple or even conflicting evidence to get a clear and reliable final-evidence, achieving the purpose of quantitative review. in order to thoroughly assess the effect of hormesis on aging, in this work, 26 papers documenting the changes of aging-related indicators induced by hormesis in Caenorhabditis elegans (a significant model organism in aging research due to its unique biological features like short life cycle, strong reproductive ability and clear genetic background) were meta-analyzed.
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, respectively. The healthspan assays showed that hormesis remarkably enhanced the bending frequency and pumping rate of worms by 28.9% and 7.0%, respectively, while effectively reduced the lipofuscin level by 15.9%. 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), 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 is highly conserved, hormesis offers the theoretical possibility of delaying intrinsic aging through exogenous intervention among humans.