ArticleAging cell2019
Hyperactivation of Nrf2 increases stress tolerance at the cost of aging acceleration due to metabolic deregulation.
Article in Aging cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 67 citations in OpenAlex.
- Article
- Metformin Partially Attenuates Simvastatin-Induced Myotoxic Responses in C2C12 Myotubes Through Metabolic Adaptation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Urolithin Α modulates inter-organellar communication via calcium-dependent mitophagy to promote healthy ageing.Autophagy · 2025Article
- Temporal Interactome Mapping of Human Tau in Drosophila Reveals Progressive Mitochondrial Engagement and Porin/VDAC1-Dependent Modulation of Toxicity.International journal of molecular sciences · 2025Article
- A novel 2-oxopyrrolidine derivative (LN-53) efficiently induces Nrf-2 signaling pathway activation in human epidermal keratinocytes.Pharmacological reports : PR · 2025Article
- Involvement of NRF2 and AMPK signaling in aging and progeria: a digest.Redox biology · 2025Review
- A novel β-TrCP1/NRF2 interaction inhibitor for effective anti-inflammatory therapy.Journal of biomedical science · 2025Article
- CHIP and aging: a key regulator of proteostasis and cellular senescence.Biogerontology · 2025Review
- 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
- Impacts of mitochondrial dysfunction on axonal microtubule bundles as a potential mechanism of neurodegeneration.Frontiers in neuroscience · 2025Review
- Exploring Greek actinobacterial biodiversity for the discovery of bioactive metabolites with skin antiaging potential.Frontiers in microbiology · 2025Article
- Article
- IQGAP1 mediates the communication between the nucleus and the mitochondria via NDUFS4 alternative splicing.NAR cancer · 2023Article
- Dietary exposure to the food preservative tert-Butylhydroquinone (tBHQ) impairs zebrafish (Danio rerio) survival, growth, organ development, and gene expression in Nrf2a-dependent and independent ways.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023Article
- Mitigation of Cardiovascular Disease and Toxicity through NRF2 Signalling.International journal of molecular sciences · 2023Review
- Loss of Kmt2c in vivo leads to EMT, mitochondrial dysfunction and improved response to lapatinib in breast cancer.Cellular and molecular life sciences : CMLS · 2023Article
- NRF2 and the Moirai: Life and Death Decisions on Cell Fates.Antioxidants & redox signaling · 2023Review
- The Regulatory Effect of Phytochemicals on Chronic Diseases by Targeting Nrf2-ARE Signaling Pathway.Antioxidants (Basel, Switzerland) · 2023Review
- PGM3 inhibition shows cooperative effects with erastin inducing pancreatic cancer cell deathFrontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
Metazoans viability depends on their ability to regulate metabolic processes and also to respond to harmful challenges by mounting anti-stress responses; these adaptations were fundamental forces during evolution. Central to anti-stress responses are a number of short-lived transcription factors that by functioning as stress sensors mobilize genomic responses aiming to eliminate stressors. We show here that increased expression of nuclear factor erythroid 2-related factor (Nrf2) in Drosophila activated cytoprotective modules and enhanced stress tolerance. However, while mild Nrf2 activation extended lifespan, high Nrf2 expression levels resulted in developmental lethality or, after inducible activation in adult flies, in altered mitochondrial bioenergetics, the appearance of Diabetes Type 1 hallmarks and aging acceleration. Genetic or dietary suppression of Insulin/IGF-like signaling (IIS) titrated Nrf2 activity to lower levels, largely normalized metabolic pathways signaling, and extended flies' lifespan. Thus, prolonged stress signaling by otherwise cytoprotective short-lived stress sensors perturbs IIS resulting in re-allocation of resources from growth and longevity to somatic preservation and stress tolerance. These findings provide a reasonable explanation of why most (if not all) cytoprotective stress sensors are short-lived proteins, and it also explains the build-in negative feedback loops (shown here for Nrf2); the low basal levels of these proteins, and why their suppressors were favored by evolution.
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Registered trials
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