It's too early to cancel the free radical theory of aging
Progeria-affected mice confirmed the link between aging and oxidative stress
Copper news
A group of Swedish, British and American scientists managed to measure the level of reactive oxygen species in the mitochondria of an aging organism for the first time. The data obtained indicate that the concentrations of reactive oxygen species in them increase significantly with age, which is a confirmation of one of the variants of the free radical theory of aging. The study report is published in the journal Aging Cell (Logan et al., In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice).
The mitochondrial free radical theory of aging explains the processes of age–related degeneration by the consequences of oxidative stress - damage caused to cells by reactive oxygen species (ROS) produced by mitochondria. Confirmation of this theory could be experimental data indicating that the production of reactive oxygen species by mitochondria really increases with age. However, until recently it was not possible to obtain them, which can partly be explained by the difficulty of carrying out such measurements in actively functioning "energy stations of the cell". At the same time, however, there was a lot of evidence that a variety of effects that reduce oxidative stress inside the mitochondria can slow down degenerative processes in an aging body.
To solve this problem, scientists used the MitoB substance synthesized by one of the co-authors of the study, Michael P. Murphy, based on lipophilic cations, first used several decades ago by Russian scientist Vladimir Skulachev to study the vital activity of mitochondria. MitoB has a selective affinity for mitochondria and is able to accumulate inside them. At the same time, when interacting with active oxygen forms, this compound is converted into the oxidized form of MitoP. According to the MitoB/MitoP ratio in the cell preparation, it is possible to determine how high the level of reactive oxygen species in mitochondria was during their lifetime.
The object for measurements were genetically modified mice devoid of a mechanism for correcting errors during replication (doubling) of mitochondrial DNA, created by another co–author of the study - Barbara Cannon. With age, mitochondrial mutations accumulate in the mitochondria of these animals, which lead to a complex of degenerative changes in various tissues (neurodegeneration, loss of muscle mass, decreased vision, sense of smell, etc.) and accelerated aging – progeria. The life expectancy of these animals is reduced several times compared to ordinary rodents.
Progeria-suffering mice of different ages received the drug MitoB, after which the ratio of this compound and its oxidized form was studied in preparations of various animal tissues. Similar measurements were carried out in groups of healthy rodents of the appropriate age. As it turned out, in young mice prone to progeria and healthy animals, the MitoP/MitoB ratio did not differ in any way. However, with age, the difference increased, especially in the tissues of the liver, heart muscle and kidneys.
As explained by Fedor Severin, a Russian scientist, head of the laboratory of the A.N. Belozersky Research Institute of Physico-Chemical Biology and a participant in the Skulachev Ions project, the result obtained by the researchers for the first time allows us to substantiate the role of reactive oxygen species in the processes associated with the aging of the body. At the same time, Severin notes, the detected increase in ROS levels in mitochondria was insufficient to cause mass cell death of various tissues observed in laboratory mice with progeria. At the same time, it is likely that it became a signal to trigger destructive processes associated, for example, with excessive activity of the immune system. This assumption is confirmed by the observations of scientists who note that in parallel with the increase in ROS levels in the organisms of aging mice, an increase in the production of a number of inflammatory mediators was observed.
"The new evidence of the role of ROS in aging obtained by the authors of this study is of particular importance for our project "Skulachev Ions", – says Severin, – We conducted our own studies with mice predisposed to progeria, created by Barbara Cannon, tested the effect of mitochondrial-directed antioxidants SkQ1 on them. The results were impressive: small concentrations of SkQ1 increased the life expectancy of these animals by 25%, and, more importantly, they almost completely relieved them of the main signs of the disease: loss of muscle mass, limited mobility, loss of hair and whiskers and other signs of aging, which usually develop in these rodents at a very early age. The difference was very easy to notice: the effect of SkQ1 was compared with a placebo, and despite the fact that the study was blind, very soon the laboratory staff began to accurately distinguish the mice that actually received the substance from the control group – the first mice remained healthy and cheerful, the second ones were senile before their eyes, as they should be. In combination with the results of the latest study by the Cannon and Murphy group, our data, which are now being prepared for publication, become a weighty evidence of the effectiveness of SkQ1 as a potential treatment for many senile diseases."
Portal "Eternal youth" http://vechnayamolodost.ru02.04.2014