PMID- 30119179 OWN - NLM STAT- MEDLINE DCOM- 20181126 LR - 20181202 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 106 DP - 2018 Oct TI - Hydrogen alleviates cellular senescence via regulation of ROS/p53/p21 pathway in bone marrow-derived mesenchymal stem cells in vivo. PG - 1126-1134 LID - S0753-3322(18)32840-3 [pii] LID - 10.1016/j.biopha.2018.07.020 [doi] AB - Senescence has become a hot point issue in recent decades and requires urgent attention. As a novel and effective antioxidant, hydrogen has been proved to alleviate cellular senescence in endothelial cells in vitro. However, the effects and mechanisms of hydrogen on senescence in vivo are still unclear. In the present study, 12-month-old Sprague Dawley (SD) rats were intraperitoneal administration of hydrogen-rich saline (HRS, 10 ml/kg). Subsequently, bone marrow-derived stem cells (BMSCs) were harvested for the detection of hydrogen antisenescence effects and mechanisms. The results showed that the number of senescence-associated beta-galactosidase (SA-beta-Gal) positive cells was reduced in BMSCs from rats treated with HRS. BMSCs in rats treated with HRS possessed a better proliferation ability, showed more effectively tri-lineage differentiation potential, and had less percentage of cells in G1 cell cycle arrest than the control cells. Additionally, HRS administration inhibited the production of intracellular reactive oxygen species (ROS) and decreased the expression of senescence-related proteins p53 and p21. Our results revealed that hydrogen could alleviate cellular senescence in vivo. And the underlying mechanism of antisenescence effects of hydrogen in BMSCs was via the ROS/p53/p21 signaling pathway. Thus, hydrogen could be a new and convenient strategy for alleviating senescence and for therapy of age-related diseases. CI - Copyright (c) 2018 Elsevier Masson SAS. All rights reserved. FAU - Zhang, Wenbo AU - Zhang W AD - First Clinical College, Chongqing Medical University, #1 Yi-Xue-Yuan Road, Chongqing, 400016, China. FAU - Huang, Chao AU - Huang C AD - Department of Anatomy, Institute of Biomedical Engineering, Second Military Medical University, #800 Xiangyin Road, Shanghai, 200433, China. FAU - Sun, Aijun AU - Sun A AD - Department of Anatomy, Institute of Biomedical Engineering, Second Military Medical University, #800 Xiangyin Road, Shanghai, 200433, China. FAU - Qiao, Liang AU - Qiao L AD - Department of Anatomy, Institute of Biomedical Engineering, Second Military Medical University, #800 Xiangyin Road, Shanghai, 200433, China. FAU - Zhang, Xi AU - Zhang X AD - Department of Anatomy, Institute of Biomedical Engineering, Second Military Medical University, #800 Xiangyin Road, Shanghai, 200433, China. FAU - Huang, Junlong AU - Huang J AD - Department of Navy Aeromedicine, Second Military Medical University, #800 Xiangyin Road, Shanghai, 200433, China. FAU - Sun, Xuejun AU - Sun X AD - Department of Navy Aeromedicine, Second Military Medical University, #800 Xiangyin Road, Shanghai, 200433, China. FAU - Yang, Xiangqun AU - Yang X AD - Department of Anatomy, Institute of Biomedical Engineering, Second Military Medical University, #800 Xiangyin Road, Shanghai, 200433, China. Electronic address: yangxq_sh@126.com. FAU - Sun, Shanquan AU - Sun S AD - Department of Anatomy, Chongqing Medical University, #1 Yi-Xue-Yuan Road, Chongqing, 400016, China. Electronic address: sunsq2151@sohu.com. LA - eng PT - Journal Article DEP - 20180717 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Antioxidants) RN - 0 (Cdkn1a protein, rat) RN - 0 (Cyclin-Dependent Kinase Inhibitor p21) RN - 0 (Reactive Oxygen Species) RN - 0 (Tumor Suppressor Protein p53) RN - 7YNJ3PO35Z (Hydrogen) SB - IM MH - Age Factors MH - Animals MH - Antioxidants/*pharmacology MH - Bone Marrow Cells/*drug effects/enzymology MH - Cell Differentiation/drug effects MH - Cell Lineage MH - Cell Proliferation/*drug effects MH - Cells, Cultured MH - Cellular Senescence/*drug effects MH - Cyclin-Dependent Kinase Inhibitor p21/*metabolism MH - Dose-Response Relationship, Drug MH - G1 Phase Cell Cycle Checkpoints/drug effects MH - Hydrogen/*pharmacology MH - Male MH - Mesenchymal Stem Cells/*drug effects/enzymology MH - Oxidative Stress/drug effects MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/*metabolism MH - Signal Transduction/drug effects MH - Time Factors MH - Tumor Suppressor Protein p53/*metabolism OTO - NOTNLM OT - Antisenescence OT - Bone marrow-derived mesenchymal stem cells OT - Hydrogen OT - ROS/p53/p21 EDAT- 2018/08/19 06:00 MHDA- 2018/11/27 06:00 CRDT- 2018/08/19 06:00 PHST- 2018/04/29 00:00 [received] PHST- 2018/07/02 00:00 [revised] PHST- 2018/07/03 00:00 [accepted] PHST- 2018/08/19 06:00 [pubmed] PHST- 2018/11/27 06:00 [medline] PHST- 2018/08/19 06:00 [entrez] AID - S0753-3322(18)32840-3 [pii] AID - 10.1016/j.biopha.2018.07.020 [doi] PST - ppublish SO - Biomed Pharmacother. 2018 Oct;106:1126-1134. doi: 10.1016/j.biopha.2018.07.020. Epub 2018 Jul 17.