Lifespan extension with mTOR inhibitors rapamycin, everolimus, and temsirolimus in Caenorhabditis elegans (Maupas, 1899)

A master regulator of longevity in all eukaryotes, the mechanistic target of rapamycin signalling pathway (mTOR) is thought to mediate certain effects of dietary restriction. The tumour suppressor pRb , whose orthologue in Caenorhabditis elegans is lin-35/pRb , is predicted to be involved in almost all human cancers. As lin-35 is linked to cancer -associated pRb function in mammals and also has a tumour suppressor effect by inhibiting mTOR signalling, the lin-35 was included in the study to investigate the effects of mTOR inhibitors. We showed that mTOR inhibitors extended the lifespan of N2 and lin-35 C. elegans by reducing fertilisation efficiency and resulted in reductions in the body size of worms. Additionally, rsks-1/S6K and let-363/TOR expressions increased in the presence of rapamycin, temsirolimus, or everolimus. The elucidation of molecular mechanisms of rapamycin and its analogues regulating health prolonging will expand their therapeutic applicability in treatment of human aging and age -related disorders.