ArticleNature communications2022
Grainyhead 1 acts as a drug-inducible conserved transcriptional regulator linked to insulin signaling and lifespan.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Predicting and finding geroprotective compounds through modulating conserved longevity-associated aging modules.Science advances · 2026Article
- An atlas of thebioRxiv : the preprint server for biology · 2026Article
- Transfer RNA-derived small RNA-Gly activates the ACPH/GRHL1 axis to facilitate liver cell regeneration in acute-on chronic liver failure.Science China. Life sciences · 2026Article
- Alternol-Induced Oxidative Modification of SQSTM1/p62 Is Associated with Nrf2 Signaling and Autophagy-Related Responses in Prostate Cancer Cells.Antioxidants (Basel, Switzerland) · 2026Article
- KMT2C and KMT2D amplify GRHL2-driven enhancer activation.bioRxiv : the preprint server for biology · 2026Article
- Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins.Nature communications · 2025Article
- AICAr Inhibition of cardiomyocyte autophagy promotes p62-dependent NRF2 expression and protection against doxorubicin toxicity.Cellular and molecular life sciences : CMLS · 2025Article
- Enhancing Late-Life Survival and Mobility via Mitohormesis by Reducing Mitochondrial Calcium Levels.Aging cell · 2025Article
- Oleanolic Acid Slows Down Aging Through IGF-1 Affecting the PI3K/AKT/mTOR Signaling Pathway.Molecules (Basel, Switzerland) · 2025Article
- A naturally occurring polyacetylene isolated from carrots promotes health and delays signatures of aging.Nature communications · 2023Article
- Recent Progress in Regulation of Aging by Insulin/IGF-1 Signaling inMolecules and cells · 2022Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Aging is impacted by interventions across species, often converging on metabolic pathways. Transcription factors regulate longevity yet approaches for their pharmacological modulation to exert geroprotection remain sparse. We show that increased expression of the transcription factor Grainyhead 1 (GRH-1) promotes lifespan and pathogen resistance in Caenorhabditis elegans. A compound screen identifies FDA-approved drugs able to activate human GRHL1 and promote nematodal GRH-1-dependent longevity. GRHL1 activity is regulated by post-translational lysine methylation and the phosphoinositide (PI) 3-kinase C2A. Consistently, nematodal longevity following impairment of the PI 3-kinase or insulin/IGF-1 receptor requires grh-1. In BXD mice, Grhl1 expression is positively correlated with lifespan and insulin sensitivity. In humans, GRHL1 expression positively correlates with insulin receptor signaling and also with lifespan. Fasting blood glucose levels, including in individuals with type 2 diabetes, are negatively correlated with GRHL1 expression. Thereby, GRH-1/GRHL1 is identified as a pharmacologically malleable transcription factor impacting insulin signaling and lifespan.
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