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Genetics, Vol. 152, 179-190, May 1999, Copyright © 1999

Interorganelle Signaling Is a Determinant of Longevity in Saccharomyces cerevisiae

Paul A. Kirchmana, Sangkyu Kima, Chi-Yung Laia, and S. Michal Jazwinskia
a Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans, Louisiana 70112

Corresponding author: S. Michal Jazwinski, Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, 1901 Perdido St., Box P7-2, New Orleans, LA 70112., sjazwi{at}lsumc.edu (E-mail)

Communicating editor: A. P. MITCHELL

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




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