Anti-aging therapy and eye drops
Stop aging
Futurologists have a lot of assumptions about which technologies will reveal the secrets of life extension to people. Meanwhile, one of the most promising projects in the field of anti-aging therapy is being successfully implemented by Russian scientists.
Getting old… The rapid increase in the average age of the population is one of the most serious problems of our time.
The share of elderly people among the inhabitants of the planet has been steadily increasing since the middle of the last century. If the current trend continues in the foreseeable future, citizens of retirement and pre-retirement age will make up the majority in all developed countries without exception. In such a situation, the emergence of effective preventive and therapeutic strategies that allow you to lead a full and active life in old age becomes truly a matter of preserving social and economic well-being.
Nowadays, there is no shortage of technologies that theoretically promise to extend the basic functions of the human body indefinitely. This includes the use of stem cells (ESCs, iPSCs), therapeutic cloning with xenotransplantation, genetic manipulation and much more. However, so far their use has not led to a victory over age. This can be partly explained by safety problems and unresolved ethical issues, but the main difficulty lies in the complexity and multifactorial nature of the causes that trigger the aging processes at the cellular and molecular level.
Why is this happening There are several competing theories of aging.
One of the latter was proposed by the outstanding Russian biochemist Vladimir Petrovich Skulachev in a paper published in collaboration with V. Longo and J. By Mitteldorf in the journal Nature (November 2005). The authors of the publication highlight several points that allow us to understand this complex process in a new way.
- Firstly, aging is proposed to be considered as a program of self-destruction of the organism, set genetically and necessary to accelerate evolution. Losing its functions and dying, an adult individual gives way to other, more promising from the point of view of species conservation, relatives.
- Secondly, at the molecular level, the aging process is expressed in a violation of the structure of proteins, DNA and other biopolymers necessary for the normal functioning of the cell.
- The reason for these changes is the destructive effect of reactive oxygen species (ROS), formed mainly during redox reactions in the "power stations" of the cell - mitochondria.
- Damage to cellular structures – first of all, the mitochondria themselves, triggers the process of suicide (apoptosis) of cells, leading to the gradual extinction of vital functions of the body.
And what if we are not ready to sacrifice ourselves for the sake of further evolutionary development? Is it possible to cancel the self-destruction programmed by nature, or at least slow it down?
The perfect antioxidant So, the destructive processes occurring with age are directly related to the negative effects of reactive oxygen species, or free radicals.
Theoretically, antioxidants that neutralize ROS – vitamins C and E, beta-carotene, N-acetylcysteine, etc. – should effectively protect the body from aging and age-related diseases. In fact, they are part of many dietary supplements, health nutrition and anti-aging cosmetics, the revenues from the trade of which amount to billions of dollars a year. However, serious studies have not revealed a link between the consumption of all these products and life expectancy, as well as the frequency of various signs of aging.
Why do conventional antioxidants not work, and what can increase their effectiveness? According to V.P. Skulachev, the solution lies in the targeted delivery of antioxidants directly to the mitochondria. After all, it is in these cell structures that most of the reactive oxygen species are produced, and it is here that they cause the most significant damage.
Is it possible to find a "locomotive" that would provide such a delivery? As it turned out, lipophilic cations are ideally suited for this role – positively charged molecules that selectively penetrate into the mitochondria under the influence of a field created by a negatively charged inner mitochondrial membrane. In the 70s of the last century, with the help of these compounds, V.P.Skulachev proved the presence of a potential difference on the mitochondrial membrane. This important discovery brought the Soviet scientist worldwide fame, after which the name "Skulachev ions" was fixed for lipophilic cations.
An active study of the possibilities of targeted delivery of antioxidants was started by Skulachev's group in 2003. After a long search and experiments, the researchers constructed a molecule that includes a lipophilic "locomotive" combined with plastoquinone, a substance from plant chloroplasts that has powerful antioxidant properties. The compound, called SkQ1 (from Sk – Skulachev ion and quinone – quinone), differed in the direction of action, effectiveness in extremely small doses, as well as the ability to return to its original form after neutralizing free radicals.
Stages
The study of SKQ1 was initially carried out by a small group of scientists at the Lomonosov Moscow State University. They managed to obtain numerous confirmations of the extremely high biological activity of the studied compound. It became clear that we are talking about a potential drug or a whole group of drugs for the treatment and prevention of diseases associated with age-related changes. This made it possible to expand the project and attract sponsors and investors – first the Oleg Derpaska RAInKo Foundation, since 2009 – the Rostock Group, and since 2010 - RUSNANO.
Since the mid-2000s, the results of SkQ1 research have been regularly published in both domestic and foreign scientific publications. The articles of the project participants were published in the Proceedings of the National Academy of Sciences USA, Biochimica et Biophysica Acta (Bioenergetics), Cell and Molecular Life Sciences, Aging, Journal of Membrane Biology, FEBS Letters and others.
Now, in addition to Lomonosov Moscow State University, leading scientific institutions of Russia and the world are participating in the project: the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, the N.N. Petrov Institute of Oncology, the Faculty of Biology of Stockholm University, several American research companies (WIL Laboratories, Toxicon, ComBio), as well as most of the leading ophthalmological clinics Russia (more on this below).
The first swallow The first success of the project was the discovery made during the study of the effect of SkQ on the aging process of a special line of OXYS rats – especially sensitive to oxidative damage.
Scientists noticed that in the group of animals fed with SkQ, eye diseases characteristic of these rats did not develop with age – cataracts, retinal degeneration, dry eye syndrome. At that moment, the idea arose to first create an ophthalmic drug – eye drops. Due to the unique properties of SkQ, it can penetrate into all eye tissues after topical application – instillation. This minimizes the likelihood of side effects (since the substance does not spread throughout the body) and, accordingly, fundamentally reduces the development period of the drug. However, it still took about 5 years – it was necessary to pass all the mandatory stages of testing on animals and on volunteer patients.
As a result, in the summer of 2012, after a full cycle of clinical trials and obtaining all the necessary registration documents, the first medicine for people was admitted to the Russian market – Visomitin eye drops for the treatment of dry eye syndrome. The active substance of these drops is the same unique mitochondrial antioxidant SkQ1 (its formal chemical name is PDTF, socr. from plastoquinonyldecyltriphenylphosphonium bromide). The project does not stop there and continues clinical studies of Visomitin for other indications – cataract, glaucoma, retinal degeneration. The developers hope to repeat the success of preclinical tests already on humans and then these diseases will add to the list of indications in the instructions for Visomitin.
The prospects In the near future, the creators of the project are planning to develop a fundamentally new class of drugs with geroprotective properties.
Negotiations are already underway with representatives of Big Pharma on the conditions for the withdrawal of these drugs to the US and EU markets. So it is likely that the world's first cure for old age will be introduced into clinical practice by Russian scientists.
Portal "Eternal youth" http://vechnayamolodost.ru16.05.2013