An open access paper: "The notion that autophagy increases longevity is well illustrated by experiments in which the massive induction of autophagy by either pharmacological methods (such as the administration of rapamycin [Rapa] or spermidine) or genetic manipulations (like the knockdown the autophagy inhibitor p53) improves organismal survival and hence reduces age-associated mortality. Caloric restriction (which is the most physiological inducer of autophagy), Rapa (which is the best characterized pharmacological inducer of autophagy), or knockdown of the p53 ortholog cep-1, all extend the lifespan of the nematode Caenorhabditis elegans only when the autophagic machinery is intact. Thus, knockdown of AuTophaGy-related (atg) genes annihilates the longevity-enhancing effect of caloric restriction, Rapa, and p53 depletion. ... Similarly, it has been found that the lifespan-extending properties of the natural polyamine spermidine strictly rely on the activation of the autophagic program in several model organisms including yeast, nematodes, and flies."