ArticleFree radical biology & medicine2014
Nrf2 deficiency promotes apoptosis and impairs PAX7/MyoD expression in aging skeletal muscle cells.
Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Polyphenol supplementation boosts aerobic endurance in athletes: systematic review.Frontiers in physiology · 2024Pooled it
- Deuterated polyunsaturated fatty acids alleviate in vitro skeletal muscle dysfunction induced by oxidative stress.Free radical biology & medicine · 2026Article
- Motor reaction time in older women with different degrees of sarcopenia: What do electroencephalograms show?Einstein (Sao Paulo, Brazil) · 2026Observational
- Deuterated Polyunsaturated Fatty Acids AlleviatebioRxiv : the preprint server for biology · 2025Article
- Non-canonical roles of Keap1/Nrf2 in regulating quiescence and early activation in adult muscle stem cells.Nature communications · 2025Article
- Time to Reset: The Interplay Between Circadian Rhythms and Redox Homeostasis in Skeletal Muscle Ageing and Systemic Health.Antioxidants (Basel, Switzerland) · 2025Review
- Perspectives on mitochondrial dysfunction in the regeneration of aging skeletal muscle.Cellular & molecular biology letters · 2025Review
- Fecal Microbiota Transplantation from Mice Receiving Magnetic Mitohormesis Treatment Reverses High-Fat Diet-Induced Metabolic and Osteogenic Dysfunction.International journal of molecular sciences · 2025Article
- Muscle-specific Keap1 deletion enhances force production but does not prevent inactivity-induced muscle atrophy in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Reactive oxygen species in the pathogenesis of sarcopenia.Free radical biology & medicine · 2025Review
- Review
- Targeting Crosstalk of Signaling Pathways among Muscles-Bone-Adipose Tissue: A Promising Therapeutic Approach for Sarcopenia.Aging and disease · 2024Review
- Cystine/glutamate antiporter xCT controls skeletal muscle glutathione redox, bioenergetics and differentiation.Redox biology · 2024Article
- The Association of Methylation Status and Expression Level ofInternational journal of hematology-oncology and stem cell research · 2023Article
- The Contribution of the Nrf2/ARE System to Mechanotransduction in Musculoskeletal and Periodontal Tissues.International journal of molecular sciences · 2023Review
- Propolis Ethanolic Extract Attenuates D-gal-induced C2C12 Cell Injury by Modulating Nrf2/HO-1 and p38/p53 Signaling Pathways.International journal of molecular sciences · 2023Article
- Transcription factor NRF2 as potential therapeutic target for preventing muscle wasting in aging chronic kidney disease patients.Journal of nephrology · 2022Review
- Article
- The Nrf2 antioxidant defense system in intervertebral disc degeneration: Molecular insights.Experimental & molecular medicine · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Skeletal muscle redox homeostasis is transcriptionally regulated by nuclear erythroid-2-p45-related factor-2 (Nrf2). We recently demonstrated that age-associated stress impairs Nrf2-ARE (antioxidant-response element) transcriptional signaling. Here, we hypothesize that age-dependent decline or genetic ablation of Nrf2 leads to accelerated apoptosis and skeletal muscle degeneration. Under basal-physiological conditions, disruption of Nrf2 significantly downregulates antioxidants and causes oxidative stress. Surprisingly, Nrf2-null mice had enhanced antioxidant capacity identical to wild-type (WT) upon acute endurance exercise stress (AEES), suggesting activation of Nrf2-independent mechanisms (i.e., PGC1α) against oxidative stress. Analysis of prosurvival pathways in the basal state reveals decreased AKT levels, whereas p-p53, a repressor of AKT, was increased in Nrf2-null vs WT mice. Upon AEES, AKT and p-AKT levels were significantly (p < 0.001) increased (>10-fold) along with profound downregulation of p-p53 (p < 0.01) in Nrf2-null vs WT skeletal muscle, indicating the onset of prosurvival mechanisms to compensate for the loss of Nrf2 signaling. However, we found a decreased stem cell population (PAX7) and MyoD expression (differentiation) along with profound activation of ubiquitin and apoptotic pathways in Nrf2-null vs WT mice upon AEES, suggesting that compensatory prosurvival mechanisms failed to overcome the programmed cell death and degeneration in skeletal muscle. Further, the impaired regeneration was sustained in Nrf2-null vs WT mice after 1 week of post-AEES recovery. In an age-associated oxidative stress condition, ablation of Nrf2 results in induction of apoptosis and impaired muscle regeneration.
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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.