Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways
Hani Atamna1, Andy Nguyen, Carla Schultz, Kathleen Boyle, Justin Newberry, Hiroyuki Kato and Bruce N. Ames Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, California, USA
Methylene blue (MB) has been used clinically for about a century to treat numerous ailments. We show that MB and other diaminophenothiazines extend the life span of human IMR90 fibroblasts in tissue culture by >20 population doubling (PDLs).
MB delays senescence at nM levels in IMR90 by enhancing mitochondrial function. MB increases mitochondrial complex IV by 30%, enhances cellular oxygen consumption by 37–70%, increases heme synthesis, and reverses premature senescence caused by H2O2 or cadmium.
MB also induces phase-2 antioxidant enzymes in hepG2 cells. Flavin-dependent enzymes are known to use NAD(P)H to reduce MB to leucomethylene blue (MBH2), whereas cytochrome c reoxidizes MBH2 to MB. Experiments on lysates from rat liver mitochondria suggest the ratio MB/cytochrome c is important for the protective actions of MB.
We propose that the cellular senescence delay caused by MB is due to cycling between MB and MBH2 in mitochondria, which may partly explain the increase in specific mitochondrial activities. Cycling of MB between oxidized and reduced forms may block oxidant production by mitochondria. Mitochondrial dysfunction and oxidative stress are thought to be key aberrations that lead to cellular senescence and aging. MB may be useful to delay mitochondrial dysfunction with aging and the decrease in complex IV in Alzheimer disease.
—Atamna, H., Nguyen, A., Schultz, C., Boyle, K., Newberry, J., Kato, H., Ames, B. N. Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways.
More info: https://wiki.brown.edu/confluence/download/attachments/24806537/methylene+blue.pdf
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Methylene blue is a monoamine oxidase inhibitor (MAOI), and if infused intravenously at doses exceeding 5 mg/kg, may precipitate serious serotonin toxicity, serotonin syndrome, if combined with any selective serotonin reuptake inhibitors (SSRIs) or other serotonin reuptake inhibitor (e.g., duloxetine, sibutramine, venlafaxine, clomipramine, imipramine).
Methylene blue is also structurally similar to the chlorpromazine and the typical antipsychotics. It is the basic compound from which chlorpromazine and many other antipsychotics are made.