Energy and Cellular‐Defense Systems are Target for Anti‐Senescence Activity of Methylene Blue

Abstract

Methylene blue (MB) delays cellular senescence, induces complex‐IV, and activates Keap1/Nrf2. The molecular link of these effects to MB and cellular senescence is unclear. We investigated the effect of MB on specific factors that affect cell senescence. Since MB is redox‐active agent, we started by assaying its effect on NAD/NADH ratio. MB caused a transient increase in NAD/NADH. This increase triggered an investigation into the energy metabolism 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. As expected from previous results, MB‐treated cells doubled complex‐IV activity. In addition, a significant decline in cellular oxidants was measured in MB treated cells. 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 vs. transient) determines AMPK's effect on cell senescence. We found that the anti‐senescence activity of MB (transient activator of AMPK) was 8‐times higher than that of AICAR (chronic activator of AMPK). We investigated the effect of MB on cell cycle. We found that MB lacked an effect on cell cycle, indicating that an MB‐dependent change to cell cycle is unlikely to contribute to the anti‐senescence activity of MB. The current findings in conjunction with the activation of Keap1/Nrf2 suggest a synchronized activation of the energy and cellular defense cellular systems as a possible key factor in MB's potent anti‐senescence activity.Support or Funding InformationNIHAFARAmesThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.