最近参加抗衰老会议，报告题目是氢气和抗衰老，但抗衰老方面的研究其实并不多。在衰老细胞方面，有人发现氢气可对抗羟基自由基抑制细胞衰老。也有人发现氢气抗衰老可能和血红素相关。也有学者给动物氢水后观察到能抑制骨髓间充质干细胞衰老。在氢气抗衰老的动物实验方面，有几篇用氢水延长线虫寿命的工作。有一篇给果蝇含金属镁食品延长寿命的工作。也有学者用氢水给早衰老小鼠，发现能提高其认知功能。如果从抗衰老相关疾病来说，对老年性痴呆、帕金森病、代谢综合征、高血脂、高尿酸等研究，都可以算抗衰老相关研究。

在信号通路方面，比较多的研究是发现氢气能影响sirt1和mTOR通路。另外AMPK和Nrf2也是衰老密切相关的信号通路，氢气的作用也比较明确。

这些研究应该都可算是氢气和衰老的研究。我个人认为，衰老是一个程序化过程。炎症和氧化这种许多疾病共同的病理生理基础，也应是人类和动物衰老的病理基础。氢气具有抗炎症抗氧化作用，也应该对衰老产生一定延缓作用。

一、氢气抗衰老研究文献

Sakai T, Kurokawa R, Hirano S, et al. Hydrogen indirectly suppresses increases in hydrogen peroxide in cytoplasmic hydroxyl radical-induced cells and suppresses cellular senescence[J]. International journal of molecular sciences, 2019, 20(2): 456

这一研究主要是证明氢气通过血红素和羟基自由基通路发挥作用。

Hara F, Tatebe J, Watanabe I, Yamazaki J, Ikeda T, Morita T. Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells. Circ J. 2016 Aug 25;80(9):2037-46.

氢气对内皮细胞衰老的对抗作用。

Zhang W, Huang C, Sun A, Qiao L, Zhang X, Huang J, Sun X, Yang X, Sun S. Hydrogen alleviates cellular senescence via regulation of ROS/p53/p21 pathway in bone marrow-derived mesenchymal stem cells in vivo. Biomed Pharmacother. 2018 Oct;106:1126-1134.

氢气对动物骨髓间充质干细胞衰老的对抗作用。这个研究虽然是针对衰老细胞，也进行细胞培养，但给氢气是给动物。

二、氢气对动物抗衰老的研究

抗衰老研究动物一般是使用线虫、果蝇和小鼠。氢气抗衰老方面比较多的是使用线虫，果蝇和动物各有1篇。

早期氢气抗衰老是用电解氢水延长线虫寿命的研究。这里有2篇论文。

Yan H, Tian H, Kinjo T, Hamasaki T, Tomimatsu K, Nakamichi N, Teruya K, Kabayama S, Shirahata S. Extension of the lifespan of Caenorhabditis elegans by the use of electrolyzed reduced water. Biosci Biotechnol Biochem. 2010;74(10):2011-5.

Park SK, Park SK. Electrolyzed-reduced water increases resistance to oxidative stress, fertility, and lifespan via insulin/IGF-1-like signal in C. elegans. Biol Res. 2013;46(2):147-52.

使用氢水延长线虫的研究

Zhang M, Li Z, Gao D, Gong W, Gao Y, Zhang C. Hydrogen extends Caenorhabditis elegans longevity by reducing reactive oxygen species. PLoS One. 2020 Apr 22;15(4):e0231972. doi: 10.1371/journal.pone.0231972.

果蝇研究是使用金属镁添加食物。

Klichko VI, Safonov VL, Safonov MY, Radyuk SN. Supplementation with hydrogen-producing composition confers beneficial effects on physiology and life span in Drosophila. Heliyon. 2019 May 14;5(5):e01679. doi: 10.1016/j.heliyon.2019.e01679.

小鼠早衰模型主要从认知功能改善方面

Gu Y, Huang CS, Inoue T, Yamashita T, Ishida T, Kang KM, Nakao A. Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice. J Clin Biochem Nutr. 2010 May;46(3):269-76.

 

三、氢气和衰老相关信号通路研究

衰老相关信号通路最重要的有三种，分别是Sirt1、mTOR和AMPK。热量限制、白藜芦醇和NAD以及最近热卖的NMN主要是通过Sirt1通路发挥作用。mTOR是营养感受信号，雷帕霉素抗衰老主要通过这个通路。AMPK则是二甲双胍的菜。

氢气的研究论文中，直接涉及衰老细胞和动物抗衰老的研究并不多。但是涉及上述信号通路的文献比较多，这里列举出来，给大家参考。关于氢气抗衰老的综述目前似乎还没有。有兴趣的学者可以写一篇。

Sun Q, et al. Hydrogen alleviates hyperoxic acute lung injury related endoplasmic reticulum stress in rats through upregulation of SIRT1. Free Radic Res. 2017 Jun;51(6):622-632. 氢气对高氧诱导内质网应激，上调 SIRT1表达

Xing Z, et al. Hydrogen Rich Water Attenuates Renal Injury and Fibrosis by Regulation Transforming Growth Factor-β Induced Sirt1. Biol Pharm Bull. 2017;40(5):610-615.  氢水对肾脏纤维化和Sirt1表达

Li S,et al. Molecular hydrogen protects against ischemia-reperfusion injury in a mouse fatty liver model via regulating HO-1 and Sirt1 expression. Sci Rep. 2018 Sep 19;8(1):14019. 氢气对小鼠脂肪肝缺血再灌注损伤和Sirt1上调

Li SW, et al. Hydrogen-rich water protects against liver injury in nonalcoholic steatohepatitis through HO-1 enhancement via IL-10 and Sirt 1 signaling. Am J Physiol Gastrointest Liver Physiol. 2021 Apr 1;320(4):G450-G463. 非酒精脂肪肝

Lin CL, et al. Hydrogen-rich water attenuates amyloid β-induced cytotoxicity through upregulation of Sirt1-FoxO3a by stimulation of AMP-activated protein kinase in SK-N-MC cells. Chem Biol Interact. 2015 Oct 5;240:12-21. AMPK， 淀粉样蛋白诱导细胞毒性

Du J, Li J, Li R, Yan X. High concentration of hydrogen ameliorates lipopolysaccharide-induced acute lung injury in a sirt1-dependent manner. Respir Physiol Neurobiol. 2021 Oct 28;296:103808.

Yang S, et al. Hydrogen attenuated oxidized low-density lipoprotein-induced inflammation through the stimulation of autophagy via sirtuin 1. Exp Ther Med. 2018 Nov;16(5):4042-4048.

Qi LS, et al. Sirtuin Type 1 Mediates the Retinal Protective Effect of Hydrogen-Rich Saline Against Light-Induced Damage in Rats. Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8268-79. .

Liu Y, et al. Protective Effect of Hydrogen on Sodium Iodate-Induced Age-Related Macular Degeneration in Mice. Front Aging Neurosci. 2018 Dec 4;10:389. Sirt1 expression

Wang P, et al. Hydrogen Gas Attenuates Hypoxic-Ischemic Brain Injury via Regulation of the MAPK/HO-1/PGC-1a Pathway in Neonatal Rats. Oxid Med Cell Longev. 2020 Feb 13;2020:6978784.

Ku JY, et al. Combination of Korean Red Ginseng Extract and Hydrogen-Rich Water Improves Spermatogenesis and Sperm Motility in Male Mice. Chin J Integr Med. 2020 May;26(5):361-369.

Yan WM,et al. The reason for the amelioration of N-methyl-N-nitrosourea-induced retinitis pigmentosa in rats by hydrogen-rich saline. Int J Ophthalmol. 2017 Oct 18;10(10):1495-1503.

Zhang Z, et al. Hydrogen-saturated saline mediated neuroprotection through autophagy via PI3K/AKT/mTOR pathway in early and medium stages of rotenone-induced Parkinson's disease rats. Brain Res Bull. 2021 Jul;172:1-13.

Fu Z, et al.  Hydrogen-Rich Saline Inhibits Lipopolysaccharide-Induced Acute Lung Injury and Endothelial Dysfunction by Regulating Autophagy through mTOR/TFEB Signaling Pathway. Biomed Res Int. 2020 Jan 30;2020:9121894.

Zhuang X, et al.  Molecular hydrogen attenuates sepsis-induced neuroinflammation through regulation of microglia polarization through an mTOR-autophagy-dependent pathway. Int Immunopharmacol. 2020 Apr;81:106287.

Lu H, et al.  Molecular hydrogen regulates PTEN-AKT-mTOR signaling via ROS to alleviate peritoneal dialysis-related peritoneal fibrosis. FASEB J. 2020 Mar;34(3):4134-4146.

Yao W, et al.  MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline. Biosci Rep. 2020 Jan 31;40(1):BSR20191043. IGF- 1/PI3K/Akt/mTOR