17 February 2015

Four methods that can cure old age

Eternal youth!

Alexander Melnikov, AIF

How doctors will be able to prolong our lives and delay the arrival of old age, " says Alexey Moskalev, a specialist in the field of gerontology.

Is life twice as long?– The increase in life expectancy is real.

In laboratory studies on animals, scientists managed to extend it several times. For example, in such primitive animals as nematodes and drosophila flies, life was extended up to 10 times, in mice – up to 2 times. The probability of reproducing such effects in humans is high, since in experiments scientists manipulated those genes that humans also have. And it is already well known that it is these genes that significantly affect our life expectancy. This is evidenced by studies of the genomes of super–long-livers - people living for more than 100 years.

It is encouraging that some progress in research on mice was achieved only by therapeutic methods – with the help of pharmacological agents, life was prolonged up to 30%, and gene therapy – up to 24%. Such approaches, in case of successful clinical trials, can be used for the prevention and treatment of so-called age-dependent diseases in humans.

But I think the main role in prolonging life will be played not only by drugs or gene therapy. This requires a whole range of therapeutic and preventive approaches, which, in addition to pharmacotherapy and gene therapy, also includes cell therapy, bioengineering methods and nanotechnology. It is possible that some organs will need to be replaced with new ones created in special bioreactors from the patient's own cells. Of course, the behavior of the person himself is extremely important for increasing life expectancy – he must adhere to the correct regime of activity, rest and nutrition, including a well-balanced diet. Let's take a closer look at modern scientific approaches to life extension.

Method 1: Gene therapyOn the one hand, the role of heredity in the longevity of the average person is not very high – 25%.

On the other hand, it is known that people with hereditary longevity, living 100 years or more, often do not stand out in their lifestyle in any special way. This means that the features of their genome allow them to cope with errors and stresses associated with overeating, physical inactivity, alcohol intake, smoking. There are relatively few such people and they are closely studied by geneticists. It turned out that they have special variants of not just one gene, but a combination of a whole set of genes responsible for different functions of our body - from the speed of growth to the ability to perceive odors and the feeling of pain. That is, for a long life, you need a happy combination of different genes.

However, experiments with animals have shown that a useful mutation (change) in just one specific gene is quite sufficient to significantly prolong an animal's life. And this opens up broad prospects for gene therapy. After all, this method represents targeted changes in individual genes. Today it is being widely developed all over the world, and even the first gene therapy drugs have already appeared.

For example, in 2012, for the first time in the European Union, the drug Alipogene tiparvovec was officially approved for practical use for a rare hereditary disease – deficiency of the enzyme lipoprotein lipase. In such patients, the amount of lipids in the blood is sharply increased, this leads to early atherosclerosis of blood vessels, and heart attacks and strokes at the age of 20-25 years. In addition, such patients have severe pancreatitis – inflammation of the pancreas. The drug is a normal gene of the lipoprotein lipase enzyme, "packed" into a virus that is practically harmless to humans. The drug is injected into the body once by injection, and the virus embeds the therapeutic gene into the genome of muscle cells. As a result, they begin to produce a normal enzyme in sufficient quantities.

Most of the tools for genetic therapy are built on this principle. They are very widely and successfully used in experiments and animal studies. Many of these drugs are aimed at improving the genes associated with aging of the body. So, in 2012, Spanish scientists from the National Cancer Research Center increased the life expectancy of adult mice by injecting them with a single gene therapy drug. They built a telomerase gene into animal cells with the help of a virus – the life expectancy depends on the activity of this enzyme. As a result, mice that were injected with the drug at the age of one year lived 24% longer, and treatment started at 2 years old extended the life of animals by 13%.

While gene therapy is still rarely used in the treatment of diseases in humans. However, gene therapy drugs for the treatment of diseases such as cystic fibrosis, hereditary blindness and deafness are on the way. They are in the late stages of clinical trials, and may soon be registered. We should expect the emergence of new means for the gene therapy of senile diseases. Technologies for the creation of gene drugs based on viruses are rapidly improving, and they are becoming more effective and safe. And most likely, it will be possible to "correct" the genome in favor of longevity not only in future generations of people, but also in the living. For example, if you are a carrier of a variant of a gene predisposing to senile retinal dystrophy, then in the future it will be possible to locally "edit" it and save you from the development of this senile syndrome.

Method 2: medicines for old ageThe effectiveness of genetic methods indicates that it is possible to prolong life with the help of pharmaceuticals.

After all, scientists can purposefully create drugs that will affect both the genes themselves and the enzymes regulated by them – the drugs will activate or inhibit them, depending on the need. And by the way, some such funds already exist. Some are still being studied in laboratories, others are already being actively applied in practice. However, the instructions for them do not say that they need to be taken to prolong life – aging is not officially considered a disease. These are medicines for the treatment of various diseases, often associated with aging, but having such a happy "side effect" as prolonging life.

These drugs can be created purposefully: knowing the structure of the enzyme, you can make a medicine suitable for it in about the same way as the key to the lock. Another approach is more random: the search (screening) of a huge number of promising chemical compounds for the creation of drugs. They are collected in so-called "libraries": they are tested on yeast, nematodes, fruit flies, mice. And if there is an effect, the research continues further. All this is very promising, because today more than 200 potential geroprotectors are already known – this is the name of substances that can prolong life.

Method 3: Cell therapyToday it is already clear that stem cells can actually contribute to the rejuvenation of the body or some of its organs.

Of course, there are many scams and abuses in this area. But there are also many scientific breakthroughs. It has already been proven in serious studies that the introduction of donor stem cells into damaged areas of the brain improves the condition of stroke patients. There is no doubt that stem cells help treat coronary heart disease and increase the survival rate of patients with myocardial infarction. All these are classic age-related diseases.

The combination of cell therapy with the use of geroprotectors is very promising. Even short-term treatment of cardiac stem cells with rapamycin and resveratrol before their administration to old mice who have suffered a heart attack increases the effectiveness of treatment, and the recovery of the heart muscle occurs faster.

Previously, the use of stem cells was associated with great ethical problems caused by the use of embryonic cells from abortive material. But now techniques have been developed to obtain a sufficient number of stem cells from the patient himself.

Probably the easiest way to do this is immediately after his birth – the baby's umbilical cord blood can be frozen in liquid nitrogen and stored indefinitely, until the time when it is needed. There are already specialized cord blood banks operating on a commercial basis. But unfortunately, the number of stem cells obtained in this way is not always sufficient for the treatment of age-dependent diseases, and cell samples are often damaged and bacterial infection during storage.

Another potential source of cells for repairing damaged and aging tissues is mesenchymal stem cells concentrated in bone marrow and adipose tissue. They are obtained by puncture, and then propagated in the laboratory to obtain them in sufficient quantities.

The third way to obtain stem cells is to reprogram the mature cells of the patient himself into the semblance of embryonic stem cells. This is a very promising direction, and for the way they were obtained, the Japanese scientist Shinya Yamanaka was awarded the Nobel Prize. The use of any stem cells has several pitfalls. Apparently, they can provoke some types of cancer. In addition, in order for stem cells to mature properly and lead to tissue regeneration, they must receive special stimuli from the body itself – these are special hormones, growth factors, cytokines, signals from surrounding cells. And you need to be able to manage these processes. Research in this direction is actively underway. Without this, the effect of stem cells can be very short-lived. And stimulating the development of new cells in the brain can sometimes contribute to the forgetting of knowledge gained during life.

Method 4: Growing and transplanting organsTheoretically, any organ can be grown from embryonic stem cells.

But in reality, a lot of problems need to be solved for this. And as experience shows, they are solved quite successfully. We have already learned to grow in laboratories not only cartilage and skin tissue, blood vessels, but also hollow organs such as the ureter, bladder, uterus and vagina.

Moreover, American scientists last year successfully performed a vaginal transplant for four teenage girls for the first time. They had a rare malformation of this organ. The vagina was grown in the laboratory from the patients' own cells.

It is more difficult to grow organs such as the heart, liver or kidneys. It is even more difficult to ensure that they "fuse" with the nerves and blood vessels of the body. Such organs have a more complex structure and include many types of cells. But the experiments have produced impressive results. In 2010, a mini-spleen was collected from stem cells. Similarly, in the summer of 2013, Japanese scientists recreated the human liver tissue and implanted this miniature mouse organ, in whose body it sprouted blood vessels and worked like a real liver. For the first time, Australian scientists managed to create a fragment of a kidney from stem cells in the fall of 2013. In the winter of 2014, researchers from Texas managed to grow new lungs from stem cells. At the moment, scientists are trying to develop a technique for growing these organs so large that they can be transplanted to humans.

It is expected that artificially grown complex organs like the liver, kidneys, heart and lungs will enter medical practice in the next 15-20 years. A little later, scientists will learn how to recreate and regenerate individual brain structures. Of course, the replacement of such damaged organs can significantly prolong life.

Dossier
Alexey Alexandrovich Moskalev (born November 5, 1976) is well known among scientists studying the problem of life extension. He defended his doctoral dissertation on this topic when he was 27 years old. Now he is actively continuing research, and cooperates with leading experts from all over the world. He heads the Laboratory of Molecular Radiobiology and Gerontology of the Institute of Biology of the Komi National Research Center of the Ural Branch of the Russian Academy of Sciences, the Department of Ecology of Syktyvkar State University and the Laboratory of Genetics of Life Expectancy and Aging at the Moscow Institute of Physics and Technology (MIPT). In addition, Alexey Moskalev lectures at George Mason University (Virginia, USA) and advises international scientific foundations.

Portal "Eternal youth" http://vechnayamolodost.ru17.02.2015

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