Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells

Circ J. 2016 Aug 25;80(9):2037-46. doi: 10.1253/circj.CJ-16-0227. Epub 2016 Jul 29.


Background: Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2on endothelial senescence and clarified the mechanisms involved.

Methods and results: Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55±0.07 mmol/L. This concentration gradually decreased, and H2was almost undetectable in medium after 12 h. At 24 h after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated β-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2on HUVECs.

Conclusions: H2has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. (Circ J 2016; 80: 2037-2046).

MeSH terms

  • Cellular Senescence / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Hydrogen / metabolism*
  • NAD / metabolism*
  • NF-E2-Related Factor 2 / metabolism*
  • Polychlorinated Dibenzodioxins / pharmacology*


  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Polychlorinated Dibenzodioxins
  • NAD
  • Hydrogen