Title | Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Hu Z, Xia B, Postnikoff SDl, Shen Z-J, Tomoiaga AS, Harkness TA, Seol JHwan, Li W, Chen K, Tyler JK |
Journal | Elife |
Volume | 7 |
Date Published | 2018 08 17 |
ISSN | 2050-084X |
Keywords | Basic-Leucine Zipper Transcription Factors, Eukaryotic Initiation Factor-2, Gene Expression Regulation, Fungal, Longevity, Phosphorylation, Protein Biosynthesis, Protein-Serine-Threonine Kinases, Ribosomes, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins |
Abstract | Translational efficiency correlates with longevity, yet its role in lifespan determination remains unclear. Using ribosome profiling, translation efficiency is globally reduced during replicative aging in budding yeast by at least two mechanisms: Firstly, Ssd1 is induced during aging, sequestering mRNAs to P-bodies. Furthermore, Ssd1 overexpression in young cells reduced translation and extended lifespan, while loss of Ssd1 reduced the translational deficit of old cells and shortened lifespan. Secondly, phosphorylation of eIF2α, mediated by the stress kinase Gcn2, was elevated in old cells, contributing to the global reduction in translation without detectable induction of the downstream Gcn4 transcriptional activator. tRNA overexpression activated Gcn2 in young cells and extended lifespan in a manner dependent on Gcn4. Moreover, overexpression of Gcn4 sufficed to extend lifespan in an autophagy-dependent manner in the absence of changes in global translation, indicating that Gcn4-mediated autophagy induction is the ultimate downstream target of activated Gcn2, to extend lifespan. |
DOI | 10.7554/eLife.35551 |
Alternate Journal | Elife |
PubMed ID | 30117416 |
PubMed Central ID | PMC6097839 |
Grant List | R01 CA207109 / CA / NCI NIH HHS / United States R01 AG050660 / AG / NIA NIH HHS / United States AG050660 / / NIH Office of the Director / International CA208257 / / NIH Office of the Director / International R01 CA208257 / CA / NCI NIH HHS / United States R01 CA095641 / CA / NCI NIH HHS / United States R01 GM064475 / GM / NIGMS NIH HHS / United States CA95641 / / NIH Office of the Director / International CA207109 / / NIH Office of the Director / International |
Related Faculty:
Jessica K. Tyler, Ph.D.