Hydrogen can scavenge free radical molecules, and thus act as a form of antioxidant. Researchers here demonstrate that in action in nematode worms. Excessive levels of free radicals such as reactive oxygen species are present in older individuals, and this state of oxidative stress contributes to cell and tissue dysfunction. The role of oxidants is a complicated one, however, as they serve as signals to cellular maintenance processes. Alteration in amounts of oxidative stress frequently have counterintuitive results on health and longevity in short-lived laboratory species. Further, the size of the effect in species such as the nematodes used here is small enough that one would expect there to be little benefit to long-lived species such as our own, given that benefits to longevity from all interventions affecting cellular maintenance signaling scale down as species life span increases.
It is well known that hydrogen can effectively scavenge free radicals in vivo or in vitro and exhibit valuable antioxidant activity. Under stress such as ischemia or hypoxia in the brain, heart and other vital organs and tissues, immune cells release a large amount of reactive oxygen species (ROS), while hydrogen can selectively neutralize hydroxyl radicals and peroxynitrites, which are related to the activation of the Nrf2 signaling pathway. Hydrogen-rich saline (HRS) can also reduce the damage to important organs, tissues, and cells caused by oxidative stress. In general, hydrogen has two advantages compared with other antioxidants, such as vitamin A and vitamin C. First, hydrogen can selectively neutralize hydroxyl radicals and nitrite anions. Second, it can quickly reach the area in danger regardless of cellular barrier. The fact that antioxidants have limited therapeutic success may be because most antioxidants cannot reach specific ROS-abundant regions. Thus, hydrogen can be used as an effective antioxidant therapy owing to its ability to diffuse rapidly across cellular membranes, because it can reach and react with cytotoxic ROS and protect against oxidative damage.
The free radical aging theory, which is also called the aging oxidative stress theory, states that aging is caused by normal oxidative metabolism by-products such as ROS. Normally, the antioxidant defense system eliminates ROS, and living organisms are protected from oxidative stress. Therefore, weakening of the antioxidant defense system, which may be caused by several factors, such as aging, will lead to excess oxidative stress and senescence. The detection of hydrogen peroxide (H2O2) further suggests that aging is caused by excess ROS. In C. elegans, genes such as sod-1, sod-4, and sod-5 encode Cu/Zn-SODs, and sod-2 and sod-3 encode Fe/Mn-SODs. Therefore, mutations in sod family genes may impact defense against oxidative stress. In this study, we found that older nematodes have higher ROS levels. Interestingly, after hydrogen treatment, the ROS levels were significantly decreased, and hydrogen could significantly extend the lifespans of the N2, sod-3 and sod-5 mutant strains, by approximately 22.7%, 9.5%, and 8.7%, respectively.
In addition, aging is regulated by a variety of pathways, such as the insulin signaling pathway, the rapamycin target signaling pathway, and the caloric restriction pathway. However, our results showed that the lifespans of the daf-2 and daf-16 strains, in which these pathways are upregulated, were not affected after hydrogen treatment. Based on these data and previous reports that hydrogen is a valuable antioxidant in vitro, lifespan extension by hydrogen is mostly related to ROS levels. It seemed that exogenous hydrogen does not act through the insulin signaling pathway to produce its antiaging effects, which may result from a direct reaction with ROS in vivo.