stimulates autophagy-dependent longevity pathways in and human cells.

The medicinal fungus is used as a dietary supplement and health tonic, but whether it affects longevity remains unclear. We show here that a water extract of mycelium extends lifespan of the nematode . The extract reduces the level of fibrillarin (FIB-1), a nucleolar protein that correlates inversely with longevity in various organisms. Furthermore, treatment increases expression of the autophagosomal protein marker LGG-1, and lifespan extension is abrogated in mutant strains that lack , , or , indicating that autophagy and stress resistance pathways are required to extend lifespan. In cultured human cells, increases concentrations of the LGG-1 ortholog LC3 and reduces levels of phosphorylated mTOR, a known inhibitor of autophagy. Notably, low molecular weight compounds (<10 kDa) isolated from the water extract prolong lifespan of and the same compounds induce autophagy in human cells. These results suggest that can increase longevity by inducing autophagy and stress resistance.