SkQ's ability to protect mitochondria has been confirmed once again

"Ion Skulacheva" slowed down the accelerated aging of mice

Oleg Lischuk, N+1

Russian and Swedish scientists managed to slow down the aging of mice whose age-related changes were accelerated by mutation of mitochondria. To do this, the animals were injected with the mitochondrial antioxidant SkQ1, known as one of the "Skulachev ions". The results of the work are published in the journal Aging (Shabalina et al., Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1).

One of the proposed mechanisms of aging of the body is the age-related accumulation of mutations in mitochondria (cellular organelles responsible for the production of energy in the form of ATP during respiration). It leads to an increase in the synthesis of reactive oxygen species (ROS), or free radicals, which damage biological macromolecules, causing wear and accelerated aging of cells.

Guided by this concept, Russian scientist Vladimir Skulachev and colleagues have been conducting research since the late 1960s to slow down the aging of individual tissues and the body as a whole with the help of antioxidants (substances that neutralize ROS), which act specifically on mitochondria. The molecules of such antioxidants, called "Skulachev ions", consist of three components: the antioxidant itself (in SkQ1 its role is played by the plant compound plastoquinone) and a saturated hydrocarbon chain that connects it to a lipophilic cation (in SkQ1 it is triphenylphosphonium — three lipophilic benzene groups connected to a positively charged phosphorus atom). Lipophilicity ensures that the molecule passes through cell membranes, a positive charge directs it in the cell to negatively charged mitochondria, and the hydrocarbon chain (linker) is responsible for the correct location of the entire molecule in the mitochondrial membrane.

In experiments, such mitochondrial antioxidants slowed down cell aging in vitro and in some living organisms. According to the results of clinical trials in Russia, eye drops with SkQ1 (plastoquinoyldecyltriphenylphosphonium bromide) called "Visomitin" were registered for the treatment of xerophthalmia, or dry eye syndrome. This drug is currently undergoing clinical trials in the USA and Europe, and forms of SkQ1 for oral administration are also being investigated.

In this study, employees of the Moscow State and Stockholm University tested SkQ1 on genetically modified mice with a variant of the PolgA gene, which increases the rate of accumulation of spontaneous mutations in mitochondria. Such animals show signs of aging already at the age of 250 days and live less than a year (the average life span of ordinary laboratory mice exceeds two years). Presumably, this is due to the increased synthesis of ROS, which react with the residues of polyunsaturated fatty acids in the molecules of cardiolipin (phospholipid of the inner membranes of mitochondria), forming malonylaldehyde and 4-hydroxynonenal. These products attach to mitochondrial proteins, impairing their functions.

Mutant mice from the age of about 100 days were added to drinking water SkQ1 at a dose of about 12 micrograms per day. Animals from the control group received clean water, otherwise their living conditions and diet did not differ.

The degree of curvature of the spine, osteoporosis and baldness in modified mice receiving (Mut+SkQ1) and not receiving (Mut) the drug. Here and below are the drawings from the article in Aging.

It turned out that mice taking the drug lived significantly longer on average: 335 versus 290 days. In addition, from the age of 200-250 days, progressive signs of aging were observed in animals from the control group, such as curvature of the spine as a result of osteoporosis, hair loss, weight loss (mainly due to adipose tissue), decreased temperature, decreased mobility and oxygen consumption, changes in the heart, liver and kidneys, as well as disorders menstrual cycle in females. Taking SkQ1 significantly slowed down the development of these signs, and some of them (for example, menstrual disorders) did not manifest at all. Also, the tissues of the liver, kidneys, brain and skeletal muscles of mice taking the drug contained significantly less malonylaldehyde and 4-hydroxynonenal than in animals from the control group. In addition, SkQ1 intake reduced mitochondrial microstructure disorders in various tissues and improved the functions of isolated mitochondria.

Effect of SkQ1 intake on body weight, body fat and energy metabolism of modified mice

"As a result, the constant intake of SkQ1 with drinking water significantly and significantly increased the life expectancy and, more importantly, the duration of the healthy life of aging animals," MSU said in a press release.

Many research teams are working on the issues of prolonging a healthy life and combating aging. Significant progress in this area, however, in animal experiments, has been achieved by limiting calories consumed, inhibiting the cellular signaling pathway mTOR with rapamycin, prescribing nicotinamide triboside, pharmacological "purification" the body from old cells, the transplantation of the sex glands of young individuals and the temporary "inclusion" of genes that transform mature cells into stem cells. Experiments with stem cells and manipulations with telomeres also have certain prospects.

Portal "Eternal youth" http://vechnayamolodost.ru  21.02.2017