Figure 1.

Hypothetical modes of genetic and pharmacologic manipulations in the regulation of longevity and autophagy. Sirtuin 1 is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase that can be activated by caloric restriction, by depletion of its negative regulators (such as nicotinamide that can be depleted by overexpression of pnc-1, which encodes a pyrazinamidase/nicotinamidase (C elegan), by pharmacological activators, in particular resveratrol. Its activity can be inhibited by pharmacological inhibitors such as EX527. Autophagy can be induced by upregulation of sirtuin 1, by downregulation of p53, or by administration of spermidine or rapamycin. These measures eventually lead to organismal longevity.