The p53 family grows old

p73 and p63 are evolving members of the p53 tumor suppressor family. TAp73 is a p73 isoform with a potent transcriptional activation domain, and loss of TAp73 predisposes mice to tumor development. In this issue of Genes & Development, Rufini and colleagues (pp. 2009-2014) discuss how TAp73-null mice display an aging phenotype that is due to mitochondrial dysfunction. Specifically, decreased levels of cytochrome C oxidase subunit 4 isoform 1 (Cox4i1) impair cytochrome C oxidase (COX) function, the multimeric enzyme that executes the last step in aerobic respiration. An emerging theme is that defects in metabolism account for both cancer and aging.