Melatonin, a hormone secreted primarily from the pineal gland, plays an important role in the regulation of circadian rhythms, is a potent antioxidant and protects nuclear and mitochondrial DNA from oxidative damage.
Mitochondria are intracellular organelles, which as components of cells are responsible for generating the majority of cellular energy in the form of adenosine triphosphate (ATP). ATP is produced through various biochemical pathways including the citric acid cycle and the electron transport chain (oxidative phosphorylation). Oxidative phosphorylation, however, also generates numerous damaging free radicals, a process which is involved in inflammation, cell damage, membrane-related diseases and cellular aging.
In a new study, chronic melatonin supplementation was evaluated to determine its effect on the impairment of mitochondria in the brains of mice. The researchers added melatonin to the drinking water of mice bred for accelerated aging and evaluated brain mitochondrial function at 5 and 10 months of age. The mitochondria were evaluated for oxidative stress by measuring the levels of lipid peroxidation and the nitrite to glutathione/glutathione disulfide ratio. Glutathione is a potent endogenous antioxidant that protects cells from reactive oxygen species such as free radicals and peroxides.
The researchers also measured the activity of the enzymes glutathione peroxidase, which protects cells by converting free hydrogen peroxide to water, and glutathione reductase, an enzyme that reduces glutathione upon exposure to oxidative stress and is used as a measure of cellular toxicity. Additionally, the study evaluated the capability of the mitochondria to produce energy via oxidative phosphorylation by the electron transport chain, using measurements of the activity of the respiratory chain complexes and the ATP content of the mitochondria.
The results of the study showed that aging caused a significant decline in mitochondrial function including decreased efficiency of the electron transport chain and reduced ATP production. In addition, there was an increase in oxygen and nitrogen free radical-induced stress. When the mice were supplemented with melatonin between 1 and 10 months of age, the mitochondrial impairment was completely prevented. In fact, melatonin administration resulted in a more consistent or even increased production of ATP.
The researchers concluded, "Thus, melatonin administration as a single therapy maintained fully functioning brain mitochondria during aging, a finding with important consequences in the pathophysiology of brain aging."
Reference:
Carretero M, Escames G, Là pez LC, Venegas C, Dayoub JC, Garcà a L, Acuà a-Castroviejo D. Long-term melatonin administration protects brain mitochondria from aging. J Pineal Res. 2009 Jul 1. Published Online Ahead of Print.
