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/2017/04/13/126797.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 compared the chronological lifespan of most gene deletions of Saccharomyces cerevisiae between cells aged under restricted and non-restricted conditions. We identified 472 mutants with enhanced or diminished extension of lifespan relative to the WT. Functional analyses of such DR-genes revealed novel processes underlying lifespan extension specifically by dietary restriction. Importantly, our set of DR-genes allowed us to generate a prioritized catalogue of transcription factors, underscoring the relevance of cell-cycle control as a mechanism of chronological-lifespan extension in yeast. In particular, 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-response pathway with cell survivorship. Our global picture of the genetic players of lifespan extension by dietary restriction highlights intricate regulatory cross-talks in aging cells.