RT Journal Article
SR Electronic
T1 Genome-Wide Mechanisms of Lifespan Extension by Dietary Restriction in Yeast
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 126797
DO 10.1101/126797
A1 Sergio E. Campos
A1 Erika Garay
A1 J. Abraham Avelar-Rivas
A1 Alejandro Juárez-Reyes
A1 Alexander DeLuna
YR 2017
UL http://biorxiv.org/content/early/2017/07/17/126797.abstract
AB Dietary restriction is arguably the most promising non-pharmacological intervention to extend human life and health span. Yet, only few genetic regulators mediating the cellular response to dietary restriction are known, and the question remains which other transcription factors and regulatory pathways are involved. To gain a comprehensive view of how lifespan extension under dietary restriction is elicited, we screened the chronological lifespan of most gene deletions of Saccharomyces cerevisiae under two dietary regimens, restricted and non-restricted. We identified 472 mutants with enhanced or diminished extension of lifespan by dietary restriction. Functional analysis of such dietary-restriction genes revealed novel processes underlying longevity specifically by dietary restriction. Importantly, this set of genes allowed us to generate a prioritized catalogue of transcription factors orchestrating the dietary-restriction response, which underscored the relevance of cell-cycle arrest control as a key mechanism of chronological longevity in yeast. We show that the transcription factor Ste12 is needed for full lifespan extension and cell-cycle arrest in response to nutrient limitation; linking the pheromone/invasive growth pathway with cell survivorship. Strikingly, STE12 overexpression was sufficient to extend chronological lifespan under non-restricted conditions. Our global picture of the genetic players of longevity by dietary restriction highlights intricate regulatory cross-talks in aging cells.