Partial reprogramming by Yamanaka factors in post-mitotic cells extends lifespan in C. elegans.

The Yamanaka factors are a set of transcription factors that reprogram differentiated cells into pluripotent stem cells. We assessed whether expression of the C. elegans orthologues of Yamanaka factors alters aging and longevity in C. elegans. We performed lifespan assays and, under optimal conditions, observed a 50% increase in the median lifespan of reprogrammed animals. The Insulin/IGF-1 Signaling (IIS) pathway influences metabolism, development, and longevity, and its inhibition results in extended longevity in C. elegans. We investigated the requirement for DAF-16/FoxO, the transcription factor that mediates IIS, in Yamanaka factor-induced lifespan extension. We found that a daf-16(-) mutation did not reduce reprogramming-induced lifespan extension. Our findings suggest that Yamanaka factor-induced lifespan extension does not require cell division in somatic cells and acts through an IIS-independent mechanism.