Disease and Aging
Reactive oxygen species (ROS) are biological products of metabolism that exert both positive and negative effects on the body. ROS include free radicals like the hydroxyl radical (OH-), superoxide anion radical (O2-), nitric oxide (NO-), etc. as well as other oxidants (e.g. hydrogen peroxide (H2O2), peroxynitrite (ONOO-) singlet oxygen (O2), etc.). The primary source of ROS formation occurs via the membrane-bound NADPH oxidase enzyme complex and the electron transport chain (primarily complex 1 and 3) of the mitochondria during aerobic metabolism.
Negative & Positive Effects of ROS
Numerous articles discuss the negative consequences of ROS and their implications on virtually every disease: Immune disorders, such as diabetes mellitus, multiple sclerosis, asthma, rheumatoid arthritis, chronic inflammation, and other fatal diseases such as cardiovascular disease, cancer, neuro-degenerative diseases such as Alzheimer’s disease and Parkinson’s disease as well as ageing (perhaps due to telomere shortening).
However, a more recent understanding of ROS demonstrates that although they may have negative side effects at high levels, they are also important biological signaling molecules that exert therapeutic and protective effects against diseases, and play a pivotal role in mediating the benefits of exercise.
Because high levels of ROS are strongly implicated in the progression and pathogenesis of disease, our bodies have the ability to scavenge these ROS after they exert their beneficial signaling effects. For example, the mitochondrial-produced superoxide is dismutated to hydrogen peroxide by superoxide dismutase, which is subsequently reduced to water via the glutathione peroxidase/reductases/NADPH system. The body also uses catalase, glutathione, vitamins A, C, E, etc. to help protect against ROS-induced damage.
Not surprisingly, the body can also suffer from reductive stress which frequently goes unmentioned. Reductive stress is achieved when the concentrations of reducing agents exceeds that of oxidizing agents. This is commonly encountered with the metabolism of ethanol. It is therefore possible for "Health Fanatics" to overdose on anti-oxidants and push the body into reductive stress instead of the oxidative stress they are steadfastly trying to avoid.
Exercise can have positive or negative effects with regard to Redox effects on the body according to how it is performed. Exercise increases oxidative stress due to metabolic processes but when exercise is undertaken on a regular basis the body up-regulates it's own anti-oxidant capacity to cope with the increased demand. This improved anti-oxidant activity clearly has additional benefits when we are not exercising but are under oxidative stress in other ways. Intermittent exercise will increase the oxidative stress burden on the body but is not sufficient to up-regulate the antioxidant capability, which makes irregular exercise potentially less healthy than doing none!
As with most things, a proper balance of exercise and supplementation is best. Molecular Hydrogen offers the potential to be a safer anti-oxidant alternative due to its selective anti-oxidant behaviour.
The free radical theory of ageing was conceived by Denham Harman in the 1950s. Two sources inspired Harman:
- the rate of living theory, which holds that lifespan is an inverse function of metabolic rate which in turn is proportional to oxygen consumption, and
- Rebbeca Gershman's observation that hyperbaric oxygen toxicity and radiation toxicity could be explained by the same underlying phenomenon: oxygen free radicals.
Noting that radiation causes "mutation, cancer and ageing", Harman argued that oxygen free radicals produced during normal respiration would cause cumulative damage which would eventually lead to organismal loss of functionality, and ultimately death.
In later years, the free radical theory was expanded to include not only ageing per se, but also age-related diseases. Free radical damage within cells has been linked to a range of disorders including cancer, arthritis, atherosclerosis, Alzheimer's disease, and diabetes. There has been some evidence to suggest that free radicals and some reactive nitrogen species trigger and increase cell death mechanisms within the body such as apoptosis and in extreme cases necrosis.
In 1972, Harman modified his original theory to what has become known as the mitochondrial theory of ageing. In its current form, this theory proposes that reactive oxygen species that are produced in the mitochondria, cause damage to certain macromolecules including lipids, proteins and most importantly mitochondrial DNA. This damage then causes mutations which leads to an increase of ROS production and greatly enhances the accumulation of free radicals within cells. This mitochondrial theory has been more widely accepted that it could play a major role in contributing to the ageing process.