The Anaphase Promoting Complex and Aging: The APCs of Longevity

The molecular biology of aging has always been of extreme interest to researchers. Recent advances made through studies of model systems have greatly increased efforts to elucidate the mechanisms involved in aging. It now appears that in yeast there are two pathways controlling aging: i) the generation of extrachromosomal rDNA circles (ERCs) through the antagonistic action of Sir2p and Fob1p; and ii) the stress response pathway, regulated by the Sch9p and Tor1p kinases. The stress response pathway in higher eukaryotes is inhibited by the insulin-signaling pathway. Mutation to the AKT kinase disrupts insulin signaling and increases longevity. Yeast express orthologues of the insulin-signaling pathway, yet insulin is not a natural substrate for yeast. The yeast Sch9p is structurally and functionally related to the AKT kinase, but the remainder of the putative yeast AKT pathways is uncharacterized. Further mystery revolves around downstream targets that are directly required for longevity. Yeast provide an opportunity to investigate the function of the yeast AKT pathway at a molecular level. A potential downstream target has been identified in yeast that links the glucose and stress response pathways with lifespan: the Anaphase Promoting Complex (APC). This review will discuss the role the APC plays in established aging pathways in yeast and the implications on higher eukaryotes.