ArticleNucleic acids research2018
The longevity SNP rs2802292 uncovered: HSF1 activates stress-dependent expression of FOXO3 through an intronic enhancer.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- A meta-analysis of genome-wide association studies identifies multiple longevity genes.Nature communications · 2019Pooled it
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- PPP2R5B regulates ANPEP expression and TGEV entry via dephosphorylation of HSF1 at Ser304/Ser308.Journal of virology · 2026Article
- Serum Biochemical and Gene Expression Changes in the Spermatozoa of Buffalo Bulls Under Heat Stress.Biochemical genetics · 2026Article
- Impact ofFrontiers in cellular and infection microbiology · 2026Article
- The Protective Effect of FOXO3 rs2802292 G-Allele on Food Intake in a Southern Italian Cohort Affected by MASLD.Nutrients · 2025Article
- Exploring the Relationship of rs2802292 with Diabetes and NAFLD in a Southern Italian Cohort-Nutrihep Study.International journal of molecular sciences · 2024Article
- [Genetics, epigenetics, and environmental factors in life expectancy-What role does nature-versus-nurture play in aging?]Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2024Review
- Differential Regulation of Male-Hormones-Related Enhancers Revealed by Chromatin Accessibility and Transcriptional Profiles in Pig Liver.Biomolecules · 2024Article
- The Biomarkers in Extreme Longevity: Insights Gained from Metabolomics and Proteomics.International journal of medical sciences · 2024Review
- Association study to evaluate Foxo1 and Foxo3 gene polymorphisms in polycystic ovary syndrome: a preliminary case-control study and in silico analysis.Molecular biology reports · 2023Article
- FOXO3A-short is a novel regulator of non-oxidative glucose metabolism associated with human longevity.Aging cell · 2023Article
- Convergent genomics of longevity in rockfishes highlights the genetics of human life span variation.Science advances · 2023Article
- Association study ofFrontiers in genetics · 2023Article
- HAP1, a new revolutionary cell model for gene editing using CRISPR-Cas9.Frontiers in cell and developmental biology · 2023Review
- Genetic, Social, and Lifestyle Drivers of Healthy Aging and Longevity.Current genetic medicine reports · 2022Article
- The Association Between Longevity-Associated FOXO3 Allele and Heart Disease in Septuagenarians and Octogenarians: The SONIC Study.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- From mutation to mechanism: deciphering the molecular function of genetic variants linked to human ageing.Briefings in functional genomics · 2022Article
- Association ofCells · 2021Article
- GADD45α alleviates the CDDP resistance of SK-OV3/cddp cells via redox-mediated DNA damage.Oncology letters · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HSF and FOXO families of transcription factors play evolutionarily conserved roles in stress resistance and lifespan. In humans, the rs2802292 G-allele at FOXO3 locus has been associated with longevity in all human populations tested; moreover, its copy number correlated with reduced frequency of age-related diseases in centenarians. At the molecular level, the intronic rs2802292 G-allele correlated with increased expression of FOXO3, suggesting that FOXO3 intron 2 may represent a regulatory region. Here we show that the 90-bp sequence around the intronic single nucleotide polymorphism rs2802292 has enhancer functions, and that the rs2802292 G-allele creates a novel HSE binding site for HSF1, which induces FOXO3 expression in response to diverse stress stimuli. At the molecular level, HSF1 mediates the occurrence of a promoter-enhancer interaction at FOXO3 locus involving the 5'UTR and the rs2802292 region. These data were confirmed in various cellular models including human HAP1 isogenic cell lines (G/T). Our functional studies highlighted the importance of the HSF1-FOXO3-SOD2/CAT/GADD45A cascade in cellular stress response and survival by promoting ROS detoxification, redox balance and DNA repair. Our findings suggest the existence of an HSF1-FOXO3 axis in human cells that could be involved in stress response pathways functionally regulating lifespan and disease susceptibility.
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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.