ArticleProceedings of the National Academy of Sciences of the United States of America2015
Regulation of Nrf2 signaling and longevity in naturally long-lived rodents.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
What it found
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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.
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Who cites it
135 citing papers in PubMed, 249 citations in OpenAlex.
- Oxidative Stress in Animals: A Systematic Analysis from Signaling Pathways to Biological Effects.Life (Basel, Switzerland) · 2026Review
- Proteostasis of organelles in aging and disease.The FEBS journal · 2026Review
- NRF2 deficit prevents pathologic Tau seeding and spreading in an induced tauopathy mouse model.Redox biology · 2026Article
- Comparative physiology and biomimetics in metabolic and environmental health: what can we learn from extreme animal phenotypes?Diabetologia · 2026Review
- The road to a long lifespan in the Persian squirrel, a natural model for extended longevity: resisting free radical stress and healthy phospholipids.GeroScience · 2026Article
- Mechanisms of Protection Against Oxidative Stress During Hibernation.International journal of molecular sciences · 2026Review
- Hypoxia Increases Cardiac Proteasomal Activity and Differentially Modulates Cullin-RING E3 Ligases in the Naked Mole-RatMuscles (Basel, Switzerland) · 2026Article
- Age-related hearing loss persisted in mice that had demonstrated improved healthspan, reduced inflammaging and extended lifespan following expression of the naked mole-rat transgene for hyaluronan synthase 2.Frontiers in aging · 2026Article
- Impact of acute and chronic hypoxia on the heme oxygenase/carbon monoxide pathway in naked mole-rats (Heterocephalus glaber).The Journal of experimental biology · 2025Article
- Ignoring the planet: A critical blind spot for research on ageing.Journal of internal medicine · 2025Review
- Dermal fibroblast cultures recapitulate differences between deermice and mice in responses to a Toll-like receptor agonist.bioRxiv : the preprint server for biology · 2025Article
- Involvement of NRF2 and AMPK signaling in aging and progeria: a digest.Redox biology · 2025Review
- Unlocking longevity through the comparative biology of aging.Nature aging · 2025Review
- Gut microbiota-dependent increase in phenylacetic acid induces endothelial cell senescence during aging.Nature aging · 2025Article
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.Biomolecules · 2025Review
- Design, Synthesis, and Evaluation of Nitroxide Radical Derivatives Based on Rhein as Potential Anti-Aging Agents Targeting the Keap1-Nrf2 Pathway.Drug design, development and therapy · 2025Article
- Dermal fibroblast cultures recapitulate differences between deermice and mice in their responses to a Toll-like receptor agonist.Frontiers in immunology · 2025Article
- Role of NRF2 in Pathogenesis of Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2024Review
- NRF2 signaling pathway and telomere length in aging and age-related diseases.Molecular and cellular biochemistry · 2024Review
75 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The preternaturally long-lived naked mole-rat, like other long-lived species and experimental models of extended longevity, is resistant to both endogenous (e.g., reactive oxygen species) and environmental stressors and also resists age-related diseases such as cancer, cardiovascular disease, and neurodegeneration. The mechanisms behind the universal resilience of longer-lived organisms to stress, however, remain elusive. We hypothesize that this resilience is linked to the activity of a highly conserved transcription factor, nuclear factor erythroid 2-related factor (Nrf2). Nrf2 regulates the transcription of several hundred cytoprotective molecules, including antioxidants, detoxicants, and molecular chaperones (heat shock proteins). Nrf2 itself is tightly regulated by mechanisms that either promote its activity or increase its degradation. We used a comparative approach and examined Nrf2-signaling activity in naked mole-rats and nine other rodent species with varying maximum lifespan potential (MLSP). We found that constitutive Nrf2-signaling activity was positively correlated (P = 0.0285) with MLSP and that this activity was also manifested in high levels of downstream gene expression and activity. Surprisingly, we found that species longevity was not linked to the protein levels of Nrf2 itself, but rather showed a significant (P < 0.01) negative relationship with the regulators Kelch-like ECH-Associated Protein 1 (Keap1) and β-transducin repeat-containing protein (βTrCP), which target Nrf2 for degradation. These findings highlight the use of a comparative biology approach for the identification of evolved mechanisms that contribute to health span, aging, and longevity.
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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.