Pimozide promotes longevity via skn-1 - collagen axis in Caenorhabditis elegans

Although various monoamine antipsychotic drugs have shown potential as anti-aging agents, the role of pimozide in aging remains unclear. We found that pimozide can extend the lifespan of C. elegans, as well as its healthy lifespan, manifested by increased activity, reduced accumulation of lipofuscin, and enhanced stress resistance.

RNA-seq results showed that pimozide significantly upregulated the expression of collagen genes and induced an increase in collagen protein synthesis. Moreover, pimozide extends the lifespan of nematodes through the skn-1 pathway, while in skn-1(EU-1), the lifespan-extending effect of pimozide is eliminated. In summary, these findings indicate that pimozide can promote the health and lifespan of C. elegans through the skn-1-collagen pathway.