Icariin supplementation has been shown to improve health and the state of the gut microbiome in mice, and appears to be neuroprotective in other studies. Here researchers show that icariin extends life in nematode worms by affecting the well-studied DAF-2 gene, and to a similar degree to DAF-2 mutation. Whether all of this will translate to an interesting effect size in humans remains to be seen; other interventions that alter metabolism, particularly this area of metabolic regulation, have produced diminishing returns in longer-lived species, where there is data to directly compare.
Aging presents an increasingly significant challenge globally, driven by the growing proportion of individuals aged 60 and older. Currently, there is substantial research interest in pro-longevity interventions that target pivotal signaling pathways, aiming not only to extend lifespan but also to enhance healthspan. One particularly promising approach involves inducing a hormetic response through the utilization of natural compounds defined as hormetins. Various studies have introduced the flavonoid icariin as beneficial for age-related diseases such as cardiovascular and neurodegenerative conditions.
To validate its potential pro-longevity properties, we employed Caenorhabditis elegans as an experimental platform. The accumulated results suggest that icariin extends the lifespan of C. elegans through modulation of the DAF-2, corresponding to the insulin/IGF-1 signaling pathway in humans. Additionally, we identified increased resistance to heat and oxidative stress, modulation of lipid metabolism, improved late-life healthspan, and an extended lifespan upon icariin treatment. Consequently, a model mechanism of action was provided for icariin that involves the modulation of various players within the stress-response network. Collectively, the obtained data reveal that icariin is a potential hormetic agent with geroprotective properties that merits future developments.