Sirtuins control key nodes in the regulation of glycolysis (HIF-1α, HIF-2α, and c-Myc) and oxidative phosphorylation (PGC-1α, LKB1, and TCA enzymes). A decline in the activity of the sirtuin family of enzymes in old age is hypothesized to lead to a shift toward a predominantly glycolytic, Warburg-like metabolism that could contribute to the exponential increase in cancer susceptibility during aging.