Interorganelle signaling is a determinant of longevity in Saccharomyces cerevisiae

Replicative capacity, which is the number of times an individual cell divid es, is the measure of longevity in the yeast Saccharomyces cerevisiae. In t his study, a process that involves signaling from the mitochondrion to the nucleus, called retrograde regulation, is shown to determine yeast longevit y, and its induction resulted in postponed senescence. Activation of retrog rade regulation, by genetic and environmental means, correlated with increa sed replicative capacity in four different S. cerevisiae strains. Deletion of a gene required for the retrograde response, RTG2, eliminated the increa sed replicative capacity. RAS2, a gene previously shown to influence longev ity in yeast, interacts with retrograde regulation in setting yeast longevi ty. The molecular mechanism of aging elucidated here parallels the results of genetic studies of aging in nematodes and fruit flies, as well as the ca loric restriction paradigm in mammals, and it underscores the importance of metabolic regulation in aging, suggesting a general applicability.