ArticleNature communications2021
Mutagenesis screen uncovers lifespan extension through integrated stress response inhibition without reduced mRNA translation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Atypical Tetracyclines Promote Longevity and Ferroptotic Neuroprotection via Translation Attenuation.Aging cell · 2026Article
- Suppression rather than activation of the integrated stress response (GCN2-ATF4) pathway extends lifespan in the fly.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Phosphatidylinositol transfer protein-1 integrates insulin/IGF-1 and TOR signaling to negatively regulate lifespan and healthspan in Caenorhabditis elegans.Journal of biomedical science · 2026Article
- Host Oxidative Response Capacity Determines Longevity Outcomes of Microbial Interventions.Aging cell · 2026Article
- Atypical tetracyclines promote longevity and ferroptotic neuroprotection via translation attenuation.bioRxiv : the preprint server for biology · 2026Article
- The GCN-2/eIF-2α/ATF-4 signaling pathway is involved inVirulence · 2025Article
- Translational regulation in stress biology.Nature cell biology · 2025Review
- Biased regulation of protein synthesis and hypoxic death by a conditional raptor mutation.Current biology : CB · 2025Article
- Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans.Nature communications · 2025Article
- The translation initiation factor eIF2α regulates lipid homeostasis and metabolic aging.Aging cell · 2025Article
- Regulating translation in aging: from global to gene-specific mechanisms.EMBO reports · 2024Review
- Biology of Healthy Aging: Biological Hallmarks of Stress Resistance Related and Unrelated to Longevity in Humans.International journal of molecular sciences · 2024Article
- Timing of TORC1 inhibition dictates Pol III involvement inLife science alliance · 2024Article
- Aging and Inflammation.Cold Spring Harbor perspectives in medicine · 2024Review
- Relationships between protein degradation, cellular senescence, and organismal aging.Journal of biochemistry · 2024Review
- Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan.GeroScience · 2023Article
- The integrated stress response protects against ER stress but is not required for altered translation and lifespan from dietary restriction inFrontiers in cell and developmental biology · 2023Article
- EasymicroPublication biology · 2023Article
- IdentifyingiScience · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein homeostasis is modulated by stress response pathways and its deficiency is a hallmark of aging. The integrated stress response (ISR) is a conserved stress-signaling pathway that tunes mRNA translation via phosphorylation of the translation initiation factor eIF2. ISR activation and translation initiation are finely balanced by eIF2 kinases and by the eIF2 guanine nucleotide exchange factor eIF2B. However, the role of the ISR during aging remains poorly understood. Using a genomic mutagenesis screen for longevity in Caenorhabditis elegans, we define a role of eIF2 modulation in aging. By inhibiting the ISR, dominant mutations in eIF2B enhance protein homeostasis and increase lifespan. Consistently, full ISR inhibition using phosphorylation-defective eIF2α or pharmacological ISR inhibition prolong lifespan. Lifespan extension through impeding the ISR occurs without a reduction in overall protein synthesis. Instead, we observe changes in the translational efficiency of a subset of mRNAs, of which the putative kinase kin-35 is required for lifespan extension. Evidently, lifespan is limited by the ISR and its inhibition may provide an intervention in aging.
Indexed as
Identifiers
What OpenQuestion holds
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.