Anti-Aging

Research & Studies

Oxidative stress and aging

 

“To date, the free radical and mitochondrial theories seem to be the 2 most prominent theories on aging and have survived the test of time. Such theories claim that oxidative stress within mitochondria can lead to a vicious cycle in which damaged mitochondria produce increased amounts of reactive oxygen species, leading in turn to progressive augmentation in damage.”

 

Romano, A. D., Serviddio, G., Matthaeis, A. D., Ballanti, F., & Vendemiale, G. (2010). Oxidative stress and aging. Journal of Nephrology, 15, 29-36. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20872368

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602  

 

Oxidative stress, mitochondrial dysfunction, and aging

 

“Aging is a complex process involving a multitude of factors. Many studies have demonstrated that oxidative stress and mitochondrial dysfunction are two important factors contributing to the aging process.”

 

Hang, C., Yahui, K., & Hong, Z. (2011). Oxidative stress, mitochondrial dysfunction, and aging. Oxidative stress, mitochondrial dysfunction, and aging, 2012(646354), 1-13. doi: 10.1155/2012/646354

 

Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

 

Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases

 

“Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects.”

Ohno, K., Ito, M., Ichihara, M., & Ito, M. (2012). Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative Medicine and Cellular Longevity, 2012, 1-11. doi: 10.1155/2012/353152

 

Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles

 

“A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases.”

 

Ichihara, M., Sobue, S., Ito, M., Ito, M., Hirayama, M., & Ohno, K. (2015). Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Medical Gas Research, 5(12), 1-21. doi: 10.1186/s13618-015-0035-1

 

Platinum nanocolloid-supplemented hydrogendissolved water inhibits growth of human tongue carcinoma cells preferentially over normal cells

 

“Anti-cancer activity of Pt-nc-supplemented HD-water was shown by its preferential cell-growth inhibition to human tongue carcinoma cells HSC-4 over normal human tongue cells DOK, and might be partly attributed to HD-water-caused enhancement of Pt-nc-relevant antioxidant ability. Pt-nc-supplemented HD-water is expected as a novel agent against human tongue cancers due to its cancer progression-repressive abilities.”

 

Saitoh, Y., Yoshimura, Y., Nakano, K., Miwa, N. (2009). Platinum nanocolloid-supplemented hydrogen dissolved water inhibits growth of human tongue carcinoma cells preferentially over normal cells. Experimental Oncology, 31(3), 156-162. Retrieved from http://exp-oncology.com.ua/uploads/magazine/772.pdf?upload 

 

Hydrogen-water enhances 5-fluorouracil-induced inhibition of colon cancer

 

“Oxidative stress is involved in cancer development. Hydrogen (H2) is a potent antioxidant and exhibits anti-inflammatory and potentially anticancer-like activities. High-content hydrogen water can inhibit colon cancer, particularly in combination with 5-fluorouracil.”

 

Runtuwene, J., Amitani, H., Amitani, M., Asakawa, A., Cheng, K., & Inui, A. (2015). Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer. PeerJ, 3, 1-15. doi: 10.7717/peerj.859

 

Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease

 

“Molecular hydrogen serves as an antioxidant that reduces hydroxyl radicals, but not the other reactive oxygen and nitrogen species. This study suggests that hydrogen water is likely able to retard the development and progression of Parkinson's disease.”

 

Yuan, F., Ito, M., Fujita, Y., Ito, M., Ichihara, M., Masuda, A., . . . Ohno, K. (2009). Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson’s disease. Neuroscience Letters, 453(2), 81-85. doi: 10.1016/j.neulet.2009.02.016

 

Pilot study of H2 therapy in Parkinson's disease: A randomized double-blind placebo-controlled trial

 

“Oxidative stress is involved in the progression of Parkinson's disease (PD). Recent studies have confirmed that molecular hydrogen (H2) functions as a highly effective antioxidant in cultured cells and animal models. The results indicated that drinking H2-water was safe and well tolerated, and a significant improvement in total UPDRS scores for patients in the H2-water group was demonstrated.”

 

Yoritaka, A., Takanashi, M., Hirayama, M., Nakahara, T., Ohta, S., & Hattori, N. (2013). Pilot study of H2 therapy in Parkinson's disease: A randomized double-blind placebo-controlled trial. Movement Disorders, 28(6), 836-839. doi: 10.1002/mds.25375

 

Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

 

“Chronic oxidative stress causes neurodegenerative diseases such as Parkinson's disease (PD). The results of this study indicated that low concentration of H2 in drinking water can reduce oxidative stress in the brain. Thus, drinking H2-containing water may be useful in daily life to prevent or minimize the risk of life style-related oxidative stress and neurodegeneration.”

 

Fujita, K., Seike, T., Yutsudo, N., Ohno, M., Yamada, H., Yamaguchi, H., . . . Noda, M. (2009). Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. PLOS ONE, 4(9). 1-10. doi: 10.1371/journal.pone.0007247

 

Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson's disease in rats

 

“Lack of dose responses of hydrogen and the presence of favorable effects with hydrogen water and intermittent hydrogen gas suggest that signal modulating activities of hydrogen are likely to be instrumental in exerting a protective effect against PD.”

 

Ito, M., Hirayama, M., Yamai, K., Goto, S., Ito, M., Ichihara, M., & Ohno, K. (2012). Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson’s disease in rats. Medical Gas Research, 2(15), 1-7. doi: 10.1186/2045-9912-2-15

 

Therapeutic effects of hydrogen in animal models of Parkinson's disease

 

“Hydrogen has an ability to reduce oxidative damage and ameliorate the loss of nigrostriatal dopaminergic neuronal pathway in two experimental animal models. Thus, it is strongly suggested that hydrogen might provide a great advantage to prevent or minimize the onset and progression of PD.”

 

Fujita, K., Nakabeppu, Y., & Noda, M. (2011). Therapeutic effects of hydrogen in animal models of Parkinson's disease. Parkinson's Disease, 2011(307875), 1-9. doi: 10.4061/2011/307875

 

Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress

 

“Hydrogen-rich saline prevented Abeta-induced neuroinflammation and oxidative stress, which may contribute to the improvement of memory dysfunction in this rat model.”

 

Li, J., Wang, C., Zhang, J. H., Cai, J., Cao, Y., & Sun, X. (2010). Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress. Brain Research, 1328, 152-161. doi: 10.1016/j.brainres.2010.02.046 

 

Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease

                                

“Hydrogen-rich saline prevented amyloid beta-induced neuroinflammation and oxidative stress in this rat model.”

 

Wang, C., Li, J., Liu, Q., Yang, R., Zhang, J. H., Cao, Y., & Sun, X. (2011). Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease. Neuroscience Letters, 491(2), 127-132. doi: 10.1016/j.neulet.2011.01.022

 

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

 

“Amyloid β (Aβ) peptides are identified in cause of neurodegenerative diseases such as Alzheimer's disease (AD). Our results indicated that HRW directly counteracts oxidative damage by neutralizing excessive ROS, leading to the alleviation of Aβ-induced cell death. Our findings suggest that HRW may have potential therapeutic value to inhibit Aβ-induced neurotoxicity.”

 

Lin, C., Huang, W., Li, H., Huang, C., Hsieh, S., Lai, C., & Lu, F. (2015). 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. Chemico-Biological Interactions, 240, 12-21. doi: 10.1016/j.cbi.2015.07.013

 

Treatment with hydrogen-rich saline delays disease progression in a mouse model of amyotrophic lateral sclerosis

 

“Treatment of mutant SOD1 G93A mice with hydrogen-rich saline (HRS, i.p.) significantly delayed disease onset and prolonged survival, and attenuated loss of motor neurons and suppressed microglial and glial activation. Treatment of mutant SOD1 G93A mice with HRS inhibited the release of mitochondrial apoptogenic factors and the subsequent activation of downstream caspase-3. Furthermore, treatment of mutant SOD1 G93A mice with HRS reduced levels of protein carbonyl and 3-nitrotyrosine, and suppressed formation of reactive oxygen species (ROS), peroxynitrite, and malondialdehyde. Treatment of mutant SOD1 G93A mice with HRS preserved mitochondrial function, marked by restored activities of Complex I and IV, reduced mitochondrial ROS formation and enhanced mitochondrial adenosine triphosphate synthesis. In conclusion, hydrogen molecule may be neuroprotective against ALS, possibly through abating oxidative and nitrosative stress and preserving mitochondrial function.”

 

Zhang, Y., Li, H., Yang, C., Fan, D., Guo, D., Hu, H., . . . Pan, S. (2015). Treatment with hydrogen-rich saline delays disease progression in a mouse model of amyotrophic lateral sclerosis. Neurochemical Research, 41(4), 770-778. doi: 10.1007/s11064-015-1750-7

 

The potential utilizations of hydrogen as a promising therapeutic strategy against ocular diseases

 

“Hydrogen can modulate several biological functions, and exhibits antioxidant and anti-inflammatory effects. The ability of hydrogen to neutralize free radicals, especially the hydroxyl radicals as well as other detrimental ROS, can be utilized to treat or prevent ocular disorders related to oxidative stress.”

 

Huang, Y. F., Tao, Y., Geng, L., Xu, W., Peng, G., & Qin, L. (2016). The potential utilizations of hydrogen as a promising therapeutic strategy against ocular diseases. Therapeutics and Clinical Risk Management, 12, 799-806. doi: 10.2147/tcrm.s102518

 

Hydrogen protects auditory hair cells from free radicals

 

“Incubation with a hydrogen-saturated medium significantly reduced ROS generation and subsequent lipid peroxidation in the auditory epithelia, leading to increased survival of the hair cells. These findings show the potential of hydrogen to protect auditory hair cells from ROS-induced damage.”

 

Kikkawa, Y. S., Nakagawa, T., Horie, R. T., & Ito, J. (2009). Hydrogen protects auditory hair cells from free radicals. NeuroReport, 20(7), 689-694. doi: 10.1097/wnr.0b013e32832a5c68

 

Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577  

Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

 

Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury

 

“Inhalation of H(2) gas at incombustible levels during ischemia and reperfusion reduces infarct size without altering hemodynamic parameters, thereby preventing deleterious left ventricular remodeling. Thus, inhalation of H(2) gas is promising strategy to alleviate ischemia-reperfusion injury coincident with recanalization of coronary artery.”

 

Hayashida, K., Sano, M., Ohsawa, I., Shinmura, K., Tamaki, K., Kimura, K., . . . Fukuda, K. (2008). Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia–reperfusion injury. Biochemical and Biophysical Research Communications, 373(1), 30-35. doi: 10.1016/j.bbrc.2008.05.165

 

Cardioprotective effect of hydrogen-rich saline on isoproterenol-induced myocardial infarction in rats

“From these results, hydrogen-rich saline exerts cardiovascular protective effects against isoproterenol-induced myocardial infarction at least in part via interactions which evoke antioxidant and anti-inflammatory activities.”

 

Jing, L., Wang, Y., Zhao, X., Zhao, B., Han, J., Qin, S., & Sun, X. (2015). Cardioprotective effect of hydrogen-rich saline on isoproterenol-induced myocardial infarction in rats. Heart, Lung and Circulation, 24(6), 602-610. doi: 10.1016/j.hlc.2014.11.018 

 

Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice

 

“In this study, scientists investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using mice that exhibited early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of these results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.”

 

Gu, Y., Huang, C., Inoue, T., Yamashita, T., Ishida, T., Kang, K., & Nakao, A. (2010). Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice. Journal of Clinical Biochemistry and Nutrition, 46(3), 269-276. doi: 10.3164/jcbn.10-19

 

Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice

 

“Consumption of hydrogen water ad libitum throughout this study suppressed the increase in the oxidative stress markers and prevented cognitive impairment. Continuous consumption of hydrogen water reduces oxidative stress in the brain, and prevents the stress-induced decline in learning and memory caused by chronic physical restraint. Hydrogen water may be applicable for preventive use in cognitive or other neuronal disorders.”

 

Nagata, K., Nakashima-Kamimura, N., Mikami, T., Ohsawa, I., & Ohta, S. (2008). Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology, 34(2), 501-508. doi: 10.1038/npp.2008.95

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