Longevity regulation in flies: A role for p53

The p53 gene is justly famous for its role as a tumor suppressor. Loss of its function through structural alterations (inactivating mutations, deletions) occurs in roughly half of all human cancers, making it the most frequently mutated cancer-associated gene [1]. Yet p53 does not function only to suppress cancer, as p53 homologues are present in short-lived invertebrates such as worms (Caenorhabditis elegans) and flies (Drosophila melanogaster) that do not develop cancer [2]. p53 is known as the "guardian of the genome" and plays an important role in maintaining genomic integrity in response to cellular damage and stress [3]. In response to DNA damage, p53 is activated and can induce cell cycle arrest of actively dividing cells, allowing time for repair of damage before re-entry into the cell cycle. In other cases, where damage is extensive, p53 can induce apoptosis, preventing the propagation of damaged or dysfunctional cells. It is likely that p53 protects flies and worms primarily by regulating apoptosis during embryogenesis. Yet p53 may play another role in flies as a longevity regulator, as illustrated by a paper by Helfand and colleagues in this issue [4].