ArticleNature aging2021
Perspective: Modulating the integrated stress response to slow aging and ameliorate age-related pathology.
Article in Nature aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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
53 citing papers in PubMed, 86 citations in OpenAlex.
- Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study.Aging cell · 2023Trial
- Stress granules at the crossroads of the proteostasis network.RNA biology · 2026Review
- Substrate Binding Relieves Autoinhibition of the Mammalian GCN2 Kinase.bioRxiv : the preprint server for biology · 2026Article
- The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026Review
- 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
- Sea Cucumber Collagen Peptides Exert an Anti-Skin Aging Effect by Inhibiting Endoplasmic Reticulum Stress in Fibroblasts.Foods (Basel, Switzerland) · 2026Article
- Repeat-associated non-AUG translation as a common mechanism for the polyGln ataxias.Cell reports · 2026Article
- Atypical tetracyclines promote longevity and ferroptotic neuroprotection via translation attenuation.bioRxiv : the preprint server for biology · 2026Article
- Review
- The GCN-2/eIF-2α/ATF-4 signaling pathway is involved inVirulence · 2025Article
- Excessive glycosylation drives thoracic aortic aneurysm formation through integrated stress response.European heart journal · 2025Article
- The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections.The American journal of pathology · 2025Review
- Translational regulation in stress biology.Nature cell biology · 2025Review
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- Genetic perturbation of cellular homeostasis regulates integrated stress response signaling to control Drosophila hematopoiesis.Biology open · 2025Article
- Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review.Molecular biology reports · 2025Review
- PACT prevents aberrant activation of PKR by endogenous dsRNA without sequestration.Nature communications · 2025Article
- Silencing excessive stress response of neurons - a new approach to treat neurodegeneration diseases.Acta pharmaceutica Sinica. B · 2025Article
- Gerotherapeutics: aging mechanism-based pharmaceutical and behavioral interventions to reduce cancer racial and ethnic disparities.Journal of the National Cancer Institute · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Healthy aging requires the coordination of numerous stress signaling pathways that converge on the protein homeostasis network. The Integrated Stress Response (ISR) is activated by diverse stimuli, leading to phosphorylation of the eukaryotic translation initiation factor elF2 in its α-subunit. Under replete conditions, elF2 orchestrates 5' cap-dependent mRNA translation and is thus responsible for general protein synthesis. elF2α phosphorylation, the key event of the ISR, reduces global mRNA translation while enhancing the expression of a signature set of stress response genes. Despite the critical role of protein quality control in healthy aging and in numerous longevity pathways, the role of the ISR in longevity remains largely unexplored. ISR activity increases with age, suggesting a potential link with the aging process. Although decreased protein biosynthesis, which occurs during ISR activation, have been linked to lifespan extension, recent data show that lifespan is limited by the ISR as its inhibition extends survival in nematodes and enhances cognitive function in aged mice. Here we survey how aging affects the ISR, the role of the ISR in modulating aging, and pharmacological interventions to tune the ISR. Finally, we will explore the ISR as a plausible target for clinical interventions in aging and age-related disease.
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.