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Schematic model of the role of Sirtuin-1 in autophagy. In human cells and C. elegans, Sirtuin-1 activation induced by caloric restriction, resveratrol or by the overexpression of its upstream activator pyrazinamidase/nicotinamidase (pcn-1) stimulates autophagy. This has lifespan-extending effects in nematodes, as do the knockdown of the C. elegans p53 ortholog Cep-1 and rapamycin administration, both of which trigger autophagy by Sirtuin-1-independent pathways
