| Title: | Genomewide mechanisms of chronological longevity by dietary restriction in budding yeast |
| Author(s): | Campos SE; Avelar-Rivas JA; Garay E; Juarez-Reyes A; DeLuna A; |
| Address: | "Unidad de Genomica Avanzada (Langebio), Centro de Investigacion y de Estudios Avanzados del IPN, Irapuato, Guanajuato, Mexico" |
| ISSN/ISBN: | 1474-9726 (Electronic) 1474-9718 (Print) 1474-9718 (Linking) |
| Abstract: | "Dietary restriction is arguably the most promising nonpharmacological 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 regulatory factors are involved. Here, we measured at the genomewide level the chronological lifespan of Saccharomyces cerevisiae gene deletion strains under two nitrogen source regimens, glutamine (nonrestricted) and gamma-aminobutyric acid (restricted). We identified 473 mutants with diminished or enhanced extension of lifespan. Functional analysis of such dietary restriction genes revealed novel processes underlying longevity by the nitrogen source quality, which also allowed us to generate a prioritized catalogue of transcription factors orchestrating the dietary restriction response. Importantly, deletions of transcription factors Msn2, Msn4, Snf6, Tec1, and Ste12 resulted in diminished lifespan extension and defects in cell cycle arrest upon nutrient starvation, suggesting that regulation of the cell cycle is a major mechanism of chronological longevity. We further show that STE12 overexpression is enough to extend lifespan, linking the pheromone/invasive growth pathway with cell survivorship. Our global picture of the genetic players of longevity by dietary restriction highlights intricate regulatory cross-talks in aging cells" |
| Keywords: | Caloric Restriction Longevity/*genetics Saccharomyces cerevisiae/*genetics Saccharomyces cerevisiae Proteins/*metabolism Saccharomycetales/*genetics Transcription Factors/*genetics Saccharomyces cerevisiae Ste12 aging cell cycle cell cycle arrest chronolo; |
| Notes: | "MedlineCampos, Sergio E Avelar-Rivas, J Abraham Garay, Erika Juarez-Reyes, Alejandro DeLuna, Alexander eng Research Support, Non-U.S. Gov't England 2018/03/27 Aging Cell. 2018 Jun; 17(3):e12749. doi: 10.1111/acel.12749. Epub 2018 Mar 25" |
