Youth lasted until death
Anton Obraztsov, Akado portal
One of the main mechanisms of cell aging has been blocked. Not only did the experimental animals begin to live 10% longer, they looked and felt young until the last few days.
The discovery was made by an international group of researchers led by Doctor of Biological Sciences, Professor, Academician of the Russian Academy of Sciences Vladimir Skulachev. As the academician said at a public lecture held on April 15 at the Central House of Scientists, they synthesized a molecule that blocks oxygen free radicals released by mitochondria. Tests on several animal species have shown that the SkQ1 substance given to animals with food accumulates in the inner membrane of mitochondria, where radicals are produced during cellular respiration.
Oxygen radicals are chemically extremely active. "There is literally not a single molecule, not a single structure in a living organism that they could not oxidize," said Academician Skulachev. "It's a terrible poison."
Radicals are formed in mitochondria – a kind of powerhouse of the cell. Mitochondria burn the nutrients consumed by the cell, convert the resulting energy into an electrical potential on their membrane, and then use it to create a single energy currency of the cell – adenosine triphosphate (ATP).
Mitochondria have their own mechanisms for neutralizing oxygen free radicals. However, they are imperfect, so gradually the concentration of radicals increases. Accordingly, the destruction caused by them also increases. Some breakdowns cause others, their number is growing like an avalanche, leading to a gradual deterioration of all body functions and, finally, to death.
Attempts to use antioxidants – substances that neutralize harmful radicals – have been made for a long time. These are, for example, vitamin C (ascorbic acid) and vitamin E (tocopherol). Such substances are widely used as preservatives. But, unfortunately, in a living organism, none of them gave a reliable effect even at very high concentrations, which in themselves poisoned the body. The substance synthesized by Skulachev and his colleagues is the first successfully acting antioxidant.
Success is primarily due to the ability of the new molecule to precisely penetrate into the place where oxygen free radicals are formed – into the inner membrane of mitochondria.
"The idea of a molecule penetrating through the double membrane of mitochondria was born a long time ago, in the late 1960s," says the academician. – We called this molecule an "electric locomotive". The interior of the mitochondria – the mitochondrial matrix – is negatively charged. Accordingly, the molecule must have a positively charged "locomotive" that will pull the rest of the molecule through the mitochondrial membrane. The rest is a long hydrophobic hydrocarbon tail, similar in properties to lipids. The tail is embedded in the inner membrane of the mitochondria."
Such constructions received, at the suggestion of American scientists, the name of Skulachev ions. Triphenylphosphonium was used as a "locomotive".
Then came the idea to attach antioxidants to the Skulachev ions. The first such molecule, called MitoQ, was synthesized and tested in 2001 by a group of British researchers led by Michael P. Murphy. As a "cargo" they used the natural antioxidant of mitochondria – ubiquinone. However, the first pancake turned out to be a lump: MitoQ almost did not change the picture of aging (in fact, MitoQ was not really tested on aging models, but maybe this is not essential for this text). Skulachev and his collaborators managed to uncover the cause of the failure and synthesize working ions. It turned out that MitoQ acts only in a very narrow window of concentrations. And it is almost impossible to provide exactly such a concentration in a living organism – at least because of individual differences in metabolism.
The researchers synthesized several types of molecules of the same type as Murphy, but with different antioxidants. These molecules are called SkQ (from Sk – Skulachev ion and quinone – quinone). Of these, the most effective was a compound based on plastoquinone, a natural antioxidant in plant chloroplasts. Compounds based on other antioxidants also work, but have shown worse characteristics.
All SkQ, especially SkQ1, have an effect with a much larger concentration spread. The window to get into is a thousand times larger than in the case of MitoQ.
It turned out that SkQ1 (and weaker, other similar substances) slightly increases the maximum life expectancy of animals, but not by more than one tenth. But the dynamics of mortality and aging with SkQ1 consumption changes radically. Usually animals age gradually, starting from the age of puberty. There are more and more ailments, different body systems are failing, protection from infections is deteriorating, and senile decrepitude is slowly but surely taking possession of a once blooming creature. The specific signs of aging are well known to gerontologists. When using SkQ1, many of them magically disappear.
Animals remain young by all signs, including breeding, until they suddenly die. Deaths in early and middle age almost disappear, almost all animals die at the end of their maximum life span.
The developers tested the SkQ1 molecule on several animals – daphnia, mice, rats, rabbits and dogs, as well as on the podospore mushroom. In all cases, a clear effect was observed, which indicates the fundamental importance of the mechanisms affected by the artificial antioxidant.
Thus, SkQ1 does not give immortality, but gives "eternal youth" within the normal or slightly increased lifespan.
The result shows that there are other causes of death besides the accumulation of free radical oxygen.
Skulachev's substances act in extremely small concentrations – on the order of picomoles (10-12 mol). They accumulate very selectively in the mitochondria, where their concentration becomes several orders of magnitude higher. There is a certain optimum – at lower and higher concentrations, the effect decreases.
In addition to ordinary animals, the researchers experimented on mutants with progeria (premature aging) – a line of OXYS rats and a line with damage to the DNA rewriting mechanism derived by geneticists from Stockholm University (in the picture – rapidly aging mice: the lower one was a control, the upper one received SkQ1). Such studies can significantly speed up the experiments, since the life span of these mice is several times less than normal. These studies have yielded similar results. The life span of prematurely aging mice increased significantly.
"As of today, 19 different signs of aging have already been slowed down or even reversed with the help of SkQ1," Skulachev summed up. "Among them are infectious diseases, osteoporosis, retinal dystrophy, cataract, uveitis, myocardial infarction, cardiac arrhythmia, male sexual behavior disorder, female sexual cycle disorder, memory loss, baldness, graying, decreased body temperature, decreased thymus and senile depression."
The development is already used in veterinary medicine for the treatment of eye diseases of animals. A positive effect was noted in two-thirds of the hundreds of dogs subjected to experimental treatment. SkQ1 is instilled into the eyes of animals in an extremely low concentration.
The scientist warns against the immediate use of the miracle substance, pointing out the need for clinical trials and the possibility of side effects that have not yet been found.
He himself said that SkQ does not accept. "We have to work and work for now,– says Academician Skulachev. "Our research is just the first swallow on a long journey." However, he hopes that in ten years, if clinical trials give a positive result, it will already be possible to buy pills in pharmacies that, if not prolong life, at least improve its quality to the level of youth.
Portal "Eternal youth" www.vechnayamolodost.ru
21.04.2008