ArticleRedox biology2015
Combined activation of the energy and cellular-defense pathways may explain the potent anti-senescence activity of methylene blue.
Article in Redox biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer's Disease: Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial.Journal of Alzheimer's disease : JAD · 2018Trial
- Reductive Stress and Dysregulated Energy Metabolism in Schizophrenia: Mechanisms and Therapeutic Targets.Biological psychiatry · 2026Review
- Methylene blue restores NADJournal of orthopaedic translation · 2026Article
- Broccoli-derived nanovesicles protect against UVB-induced skin photoaging via integrated transcriptomic and proteomic reprogramming of redox and extracellular matrix homeostasis.Frontiers in cell and developmental biology · 2026Article
- Mitochondrial dysfunction in cellular senescence: a bridge to neurodegenerative disease.npj aging · 2025Review
- Impaired Cardiac AMPK (5'-Adenosine Monophosphate-Activated Protein Kinase) and CaJournal of the American Heart Association · 2024Article
- Targeting mitophagy for neurological disorders treatment: advances in drugs and non-drug approaches.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Brain Protection by Methylene Blue and Its Derivative, Azur B, via Activation of the Nrf2/ARE Pathway in Cisplatin-Induced Cognitive Impairment.Pharmaceuticals (Basel, Switzerland) · 2022Article
- The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence.Antioxidants (Basel, Switzerland) · 2022Review
- Article
- Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Antiferroptotic Activity of Phenothiazine Analogues: A Novel Therapeutic Strategy for Oxidative Stress Related Disease.ACS medicinal chemistry letters · 2020Article
- Methylene blue elicits non-genotoxic HJournal of applied biomedicine · 2019Article
- Methylene blue does not bypass Complex III antimycin block in mouse brain mitochondria.FEBS letters · 2019Article
- Regulation of Mitochondrial Biogenesis as a Way for Active Longevity: Interaction Between the Nrf2 and PGC-1α Signaling Pathways.Frontiers in genetics · 2019Review
- Phenothiazine antioxidants increase mitochondrial biogenesis and frataxin levels in Friedreich's ataxia cells.MedChemComm · 2018Article
- Bioenergetic bypass using cell-permeable succinate, but not methylene blue, attenuates metformin-induced lactate production.Intensive care medicine experimental · 2018Article
- Organ reserve, excess metabolic capacity, and aging.Biogerontology · 2018Review
- Modeling Prion-Like Processing of Tau Protein in Alzheimer's Disease for Pharmaceutical Development.Journal of Alzheimer's disease : JAD · 2018Review
- Anti-Aging Potentials of Methylene Blue for Human Skin Longevity.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Methylene blue (MB) delays cellular senescence, induces complex-IV, and activates Keap1/Nrf2; however, the molecular link of these effects to MB is unclear. Since MB is redox-active, we investigated its effect on the NAD/NADH ratio in IMR90 cells. The transient increase in NAD/NADH observed in MB-treated cells triggered an investigation of the energy regulator AMPK. MB induced AMPK phosphorylation in a transient pattern, which was followed by the induction of PGC1α and SURF1: both are inducers of mitochondrial and complex-IV biogenesis. Subsequently MB-treated cells exhibited >100% increase in complex-IV activity and a 28% decline in cellular oxidants. The telomeres erosion rate was also significantly lower in MB-treated cells. A previous research suggested that the pattern of AMPK activation (i.e., chronic or transient) determines the AMPK effect on cell senescence. We identified that the anti-senescence activity of MB (transient activator) was 8-times higher than that of AICAR (chronic activator). Since MB lacked an effect on cell cycle, an MB-dependent change to cell cycle is unlikely to contribute to the anti-senescence activity. The current findings in conjunction with the activation of Keap1/Nrf2 suggest a synchronized activation of the energy and cellular defense pathways as a possible key factor in MB's potent anti-senescence activity.
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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.