title: Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells.
abstract: 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.
  
  
  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).
authors.affiliation: Department of Cardiovascular Medicine, Toho University School of Medicine.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hara
authors.forename: Junko
authors.initials: J
authors.lastname: Tatebe
authors.forename: Ippei
authors.initials: I
authors.lastname: Watanabe
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamazaki
authors.forename: Takanori
authors.initials: T
authors.lastname: Ikeda
authors.forename: Toshisuke
authors.initials: T
authors.lastname: Morita
mesh_terms: D016922:Cellular Senescence / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D000072317:Polychlorinated Dibenzodioxins; D009243:NAD; D006859:Hydrogen