ArticleeLife2018
Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 90 citations in OpenAlex.
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Article
- Inhibition of the integrated stress response rescues a histidyl-tRNA synthetase variant associated with Charcot-Marie-Tooth disease.NAR molecular medicine · 2026Article
- A multi-omics molecular landscape of 30 tissues in aging female rhesus macaques.Nature methods · 2025Article
- Chromosome duplication causes premature aging via defects in ribosome quality control.PLoS biology · 2025Article
- Overexpression of Ssd1 and calorie restriction extend yeast replicative lifespan by preventing deleterious age-dependent iron uptake.bioRxiv : the preprint server for biology · 2025Article
- Protein Translation Rates Are Negatively Correlated With Lifespan in Inbred Drosophila Strains.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Investigating the role of RNA-binding protein Ssd1 in aneuploidy tolerance through network analysis.RNA (New York, N.Y.) · 2024Article
- Regulating translation in aging: from global to gene-specific mechanisms.EMBO reports · 2024Review
- The response to single-gene duplication implicates translation as a key vulnerability in aneuploid yeast.PLoS genetics · 2024Article
- Premature aging in aneuploid yeast is caused in part by aneuploidy-induced defects in Ribosome Quality Control.bioRxiv : the preprint server for biology · 2024Article
- Molecular Mechanisms of Genotype-Dependent Lifespan Variation Mediated by Caloric Restriction: Insight from Wild Yeast Isolates.bioRxiv : the preprint server for biology · 2024Article
- Induction of proteasomal activity in mammalian cells by lifespan-extending tRNA synthetase inhibitors.GeroScience · 2024Article
- Protein translation: biological processes and therapeutic strategies for human diseases.Signal transduction and targeted therapy · 2024Review
- General control nonderepressible 2 (GCN2) as a therapeutic target in age-related diseases.Frontiers in aging · 2024Review
- Molecular mechanisms of genotype-dependent lifespan variation mediated by caloric restriction: insight from wild yeast isolates.Frontiers in aging · 2024Article
- Multiomics ofInternational journal of molecular sciences · 2023Article
- Saccharomyces cerevisiae as a research tool for RNA-mediated human disease.Wiley interdisciplinary reviews. RNA · 2023Review
- Early-adulthood spike in protein translation drives aging via juvenile hormone/germline signaling.Nature communications · 2023Article
- Relationships between Secreted Aspartyl Proteinase 2 and General Control Nonderepressible 4 gene in the Candida albicans resistant to itraconazole under planktonic and biofilm conditions.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.