A major hallmark of aging, and a key driver for the onset of age-related pathophysiologies across multiple species, including primates, is the disruption of cellular redox homeostatic mechanisms that protect against a variety of environmental, oxidative, pathological, and toxicological insults. Now, a study from researchers at Oregon State University shows that a specific detoxification compound, glutathione, helps resist the toxic stresses of everyday life. The team state their findings also show that glutathione levels decline with age, which sets the stage for a wide range of age-related health problems. The opensource study is published in the journal Redox Biology.
Previous studies show that decline of detoxification pathways are linked to cardiovascular disease, diabetes and cancer, some of the primary causes of death in the developed world. It has long been known that glutathione is a strong antioxidant, whose existence appears to date back as far as oxygen-dependent, or aerobic life itself, about 1.5 billion years. It’s a principal compound to detoxify environmental stresses, air pollutants, heavy metals, pharmaceuticals and many other toxic insults. The current study shows that glutathione loss during menadione treatment is accelerated with age, and a compound known as N-acetyl-cysteine, or NAC, maintains glutathione mitigated age-related susceptibility to redox cycling menadione.
The current study uses a toxic compound called menadione to stress young and aged cells from rats to show, in the face of that stress, the younger cells lost significantly less of their glutathione than older cells did. Results show that the glutathione levels of young rat cells never decreased to less than 35% of its initial level, whereas in older rat cells glutathione levels plummeted to 10% of their original level.
Data findings show that NAC pretreatment resulted in a 2-fold reduction in cell death, suggesting that the age-related increase in menadione susceptibility likely stems from attenuated glutathione-dependent defenses. This data identifies cellular targets for intervention in order to limit age-related toxicological insults to menadione and potentially other redox cycling compounds. The lab explain that NAC is known to boost the metabolic function of glutathione and increase its rate of synthesis. They go on to add that NAC is already used in emergency medicine to help patients in a toxic crisis, such as ingestion of poisonous levels of heavy metals.
The team surmise their results show that menadione causes a rapid loss of glutathione in hepatocytes from both young and old rats, however, the rate and degree of glutathione loss is more extensive in older animals. For the future, the researchers state their research not only offers insight into why the health of animals declines with age, it specifically points to a compound that might help prevent some of the toxic processes involved.
Source: Oregon State University
