Genomewide mechanisms of chronological longevity by dietary restriction in budding yeast.

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 γ-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.

journal_name

Aging Cell

journal_title

Aging cell

authors

Campos SE,Avelar-Rivas JA,Garay E,Juárez-Reyes A,DeLuna A

doi

10.1111/acel.12749

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

e12749

issue

3

eissn

1474-9718

issn

1474-9726

journal_volume

17

pub_type

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