Alternatives to the death: how to defeat aging

As a modern molecular biology looks at the phenomenon of aging? As the aging of trying to learn whether there is hope for slowing down or even stop this process? These questions focused on the lecture biologist Alexander Panchina with which he made in the past in the office Mail.Ru Group popular science lectures Set Up.

Aging - a decrease with age life expectancy. Starting from a certain age every year increases the likelihood of a person's death. After 20 years, every eight years of life increases the risk approximately doubled. People are dying from heart disease, cancer, stroke, emphysema, pneumonia, kidney disease, Alzheimer's disease, accident. But the good news is that scientific and technological progress has allowed to win many diseases and prolong human life.

Over the past 60 years in all countries increased life expectancy, and in some people began to live about 20 years longer. In Australia, Canada, Japan and some European countries, the average life expectancy exceeds 80 years. This is the question about the importance of good medicine in the country, the wise use of scientific advances, the use of effective medicines, and not some homeopathy and so on. But in general, throughout the world is noticeable progress.



Even at the end of the XIX century has been hypothesized theoretical immortality hydra. In 1997, Daniel Martinez proved the hypothesis experimentally

When the question arises whether we can defeat this rising graph of the increase of mortality, I recall the words of the Wright brothers, "If birds can fly, then we can achieve controlled flight." Biologists say that if the hydra with age, the risk of death is not increased, it is likely that this can make us. There are no fundamental limitations that do not allow a living organism to live very long.

A classic example of a long-lived organism - the naked mole rat, who lives ten times longer than their relatives - mice and rats. Genome mole rat is already investigating scientists hoping to understand what makes it so special being and long-lived.

If we assess the diversity of life on the planet, the mammalian lifespan can vary by almost a hundred times, and animals in general - in the tens of thousands of times. With what it can be connected? It is clear that an important role in aging and longevity genes play. What a shrew or vole from an evolutionary point of view, is not particularly interested in how to live a long time. In nature, few representatives of these species survive to old age, their early enough to eat predators. Even if there was some kind of mutation, prolonging life, from her would be of little use in terms of increasing reproductive success. And the species, get rid of the threat from predators, we're just seeing an increase in life expectancy. The same naked mole rat, living under the earth, can live for 31 years. Another example of protection from predators - the ability to fly, as in the case of bats and birds. Users also can protect themselves with the help of science and technology.

Any organisms in the genome which have already been laid death program. For example, some species of salmon females die soon after spawning. But there is a more interesting example - the octopus:



Illustration: A SNAIL'S ODYSSEY

The female lays eggs octopus, stops eating and dies on average in a month. This programmed death. But it turned out that this program can be canceled, with surgically - just cut out a pair of glands, then the octopus can not live a month, and 6-9 months

. There are examples of programmed cell death, in which individual cells can kill themselves. This process is called apoptosis when cells accumulate a large number of mutations that do not become cancerous, do not pose a threat to the body, it is itself destroys, and quite reasonable - the cell is not just splashes all its contents out, and falling compartments, which can then be captured by neighbor cells and discarded.

Interestingly, there is a transition from cell death to the death of the whole organism. Gut roundworm Caenorhabditis elegans (nematode) bit fluoresces. And when the worm is dying due to natural causes or as a result of some damage, then an hour before his death in front of the bowel glow wave is amplified and gradually extends to the end of the intestine. After this, the worm moves into another world. This phenomenon is called "blue waves of death." A wave can be induced artificially, such as freezing and unfreeze the worm. Also, scientists have found a way to stop this wave. Worm life expectancy increases, but if it is damaged, it will not die from it. With the emergence of a wave starts process of cell death, but then it's blue glow is extinguished, and the worm continues to live on. Needless glow is just an indicator, and it really is the wave of cell death along the colon, which leads to

death. Why this mechanism arose? Apparently, as a result of such a "death in an hour" gets the worm as food to their own offspring. Worms nurture children, die and become food for the next generation. The symbol of the sacrifice of motherhood.

In humans, at least in adults, such mechanisms are not detected. Our aging is an aggregate of many different processes. One of them - is cell aging.

Old cells can damage nearby, can release substances that lead to inflammation. Older cells may become cancerous, and therefore would be good to get rid of them. Research results have recently been published by the removal using a special medication old cells have a certain type of genetically modified rodents. And these rodents lived longer. That is quite possible to find an approach to aging cells.

Shortening of telomeres


Human chromosomes are grayed out, the telomeres - white

The aging of cells associated with certain processes. One of them - a shortening of telomeres. That's the way nature is that every cell division the DNA molecule is shortened. At the ends of the chromosomes are segments called telomeres, which are subject to shortening, thus protecting the rest of the chromosome. Telomeres are shortened from generation to generation, and they are old cells are very short. That is, the old and the young human cells can be distinguished by the length of telomeres, taking into account certain variations in these characteristics.

However, the problem has already been solved in the shortening of our stem cells. They have the enzyme telomerase, which is able to finish building the telomeres. Therefore, about some of the cells say they are immortal.

Another great news is that we can lengthen telomeres by gene therapy. Conducted experiments in which using a special virus in the rodents delivered telomerase and telomeres were completed in the cells. These rodents, as experiments show, live longer.



44-year-old Elizabeth Parrish, head of the American research company BioViva, perhaps, became the first person in which anti-aging gene therapy

was successfully tested Similar experiments inspired by Elizabeth Parrish try to imagine such a gene therapy. It is clear that it does so within the framework of PR-campaign, because it has a large biotechnology company. The news passed the information, that's kind of like she lengthened telomeres. But this is not a scientific experiment, there is no control group, no comparison. Although the history of many inspiring and suggests that telomere shortening is not an insurmountable problem of aging.

The accumulation of damage
Another thing that happens in the cells - is the accumulation of damage. They are different. One of the types of damage - is the accumulation in the cells of junk. For example, bad crunched proteins, as it happens in the case of Alzheimer's disease. Or not operating organelles like mitochondria damaged. Each division of the damaged cells as it were diluted, and each of the resulting two cells they have to be twice less. That is, the active cell division could rejuvenate.

But the division has a dark side - a cancer. There are genetic mutations that are not diluted. Cancer cell - a cell, has accumulated a large number of mutations that can lead to divide indefinitely, disabling apoptosis. Today, there are more modern methods to fight cancer. Previously, he was completely incurable disease, is now in a number of cases it is treated.

Fasting
One of the most beautiful experiments to prolong life has been associated with the study of the effect of partial starvation. The experiment was conducted in rodents. This is a graph of mortality:



Green color shows those who eat from the belly, blue spruce on 25% less, purple - 55% less, and red - on 65%. As you can see, the maximum life expectancy has increased by about 1, 5 times. Green died somewhere in three years, while the rest lived significantly longer. When all green now dead, red still alive. The impressive result. It turned out that the mechanism of prolonging life through actual starvation for very different organisms, but not for all. There are those who have a partial deprivation reduces life expectancy. But in many species it is running. For example, the roundworm Caenorhabditis elegans, rats, some strains of mice, dogs, there are conflicting data regarding the macaques. In public, it is very difficult to put such experiments.

When found out, as a partial starvation prolongs the life of the worm, he found a hormone that is secreted in response to food intake. These hormones act on the receptor DAF-2 located at the cell surface, and that somehow promotes aging. If this receptor spoil, these worms live about twice as long.

When DAF-2 receptor is activated, it triggers a cascade of cellular events leading to inactivation of the protein called DAF-16. DAF-16 - this is a very important protein that regulates cell work as follows. If the food available and the DAF-16 is inactivated, the cell thinks, "Oh, zashib, food is full, it's okay, you can relax, I'm not in danger, it is possible to multiply, divide - everything is fine." If this signal is not present, ie DAF-2 is spoiled, or if there is no food, the DAF-16 is activated, the cell thinks, "What a mess, I'm dying, stress, a nightmare! We must save ourselves "- and runs a bunch of security mechanisms: mutations, from oxidative stress, heat shock, all in a row. That is DAF-16 makes the work hundreds of other genes that protect cells from various problems.

It was found that human proteins are similar to DAF-16 and DAF-2. But similar to DAF-16 protein was detected mutation. There are those with one embodiment of this protein, and there are people with another embodiment. Owners of the first embodiment (FOXO3) are much more likely to live to 90 years or more. That is, by studying the molecular mechanism of aging in worms, we can better understand how to construct mechanisms of aging in humans.

Of course, not everything that we learn about worms, can be translated to humans. For example, if we remove the germ cells of the gonad of the worm, it also activates the DAF-16, and he will live longer. But if you castrate themselves, it does not prolong your life.

Body weight
Dwarf bats can live up to 40 years. Organisms with larger weight to live longer. But there are those whose life expectancy is much higher than the calculated on the basis of their body mass. For example, people live much longer than other species with the same mass. Dwarf bats and their relatives are also long-lived. These bats showed up like the DAF-2 protein, but with specific mutations.

Apart from model organisms, scientists are exploring and mutations that occur in humans.



This young man has died at age 17, he had a premature aging syndrome called 'progeria. " It is a genetic disease that causes the appearance of early signs of aging. At a young age there are senile diseases, and people on average live 13 years. By this disease results in the mutation in the gene responsible for the synthesis of the protein lamin. This protein is responsible for the organization of the nucleus, the so-called nuclear matrix, nuclear structure. Worms age nuclear matrix breaks in cells, and this happens more slowly than, the worms live longer. Perhaps the destruction of the nuclear matrix plays an important role in human aging.


Growth hormone HGH indirectly leads to the amplification of the signal, which is transmitted through our analogue of DAF-2. If much easier, then dwarfs cells feel some effect of starvation. That pygmy mouse Yoda and his girlfriend Princess Leia:



Yoda was flawed gene that regulates the synthesis of growth hormone. He lived for four years in the laboratory - in terms of human age is more than a hundred years

.

In Ecuador, there is a population of people with a certain form of dwarfism called Laron syndrome, there are about a hundred people. We do not know how they live. Scientists watching them for over 20 years and was the publication that these people have reduced the risk of some senile diseases, including cancer and diabetes. Maybe they really do live longer, compared with other inhabitants of the same region.

God TOR, lord garbage


Illustration: The Ban Lab

Our cells are able to remove themselves from the garbage not only in the division. They can absorb it. This is called autophagy - cells digest the dirtiest in itself, then it somehow recover and throw. This process can help to rejuvenate cells, but prevents him TOR protein.

What is he doing? He says: "Everything is useful. This stale sandwich that you have here is handy. It will be hungry to be a blockade, and he will go to the cause. " Our ancestors lived in a regular food shortages. There were no genetically modified organisms, there was no green revolution, normal agriculture, there was nothing. Hunger could occur at any time, and, therefore, TOR has played an important role. But now this debris accumulates and damages cells. Fortunately, there are substances inhibitors that can suppress the protein.

TOR inhibitors trigger autophagy through the protein. TOR itself is named after the rapamycin: Target Of Rapamycin (target of rapamycin). Rapamycin - is an antibiotic that produce mushrooms, it is also used as an immunosuppressant. This substance is used in organ transplantation to reduce the risk of rejection. Also, rapamycin extends the life of various organisms, such as mice, and quite strongly.

Rapamycin is very expensive, so in many cases use much cheaper inhibitor of TOR - caffeine. Animal studies have confirmed that it improves and extends the life of autophagy. There are also the results of epidemiological studies, according to which human populations, where to drink a few cups of coffee a day, the mortality rate has been reduced by 10%.

There is the concept of the "French paradox": the French long-lived and rarely suffer from cardiovascular disease. At one time, it explained the consumption of resveratrol contained in red wine. Rodents this substance prolongs life. But then counted how much to consume wine man to resveratrol had the same effect - two barrels per day. Apparently, the French paradox soon linked to by ethanol, which in certain low concentrations extended the life of nematodes. In people who drink a glass of wine per day, also reduces the risk of cardiovascular diseases such as coronary heart disease, coronary heart disease and so on. But ethanol has a negative side side: alcoholism, cirrhosis of the liver, increases the risk of certain cancers. Therefore, whether it is possible to recommend a geroprotector ethanol - is a moot point

. Interestingly scientists and metformin - a cure for diabetes. It has some side effects associated with the gastrointestinal tract. There is research that confirms that metformin prolongs the life of worms.

But the longest - 50% - live nematodes thanks to alpha-ketoglutarate. It is remarkable that in humans is present in large quantities and has a low toxicity. But until now, no studies on rodents, scientists because it is very difficult to get funding to study this medicine against aging, because aging is not considered a disease. Alpha-ketoglutarate, by the way, the athletes are used as a food additive to accelerate muscle growth. But there are conflicting reports whether it really helps in this.

Young blood


Illustration: Popular Science

In one study, researchers surgically connected the bodies of two rodents - old and young, their blood pooling system. В этих условиях старый грызун живёт дольше, а молодой — меньше, при этом у старых грызунов повышается пластичность нервной системы, то есть способность нервных клеток образовывать новые нервные связи. У них даже улучшается регенерация мышечной ткани. Понятно, что никто не предлагает сшивать вместе пенсионеров и маленьких детей, чтобы пенсионеры жили дольше. Но, может быть, мы найдём какие-то факторы, которые присутствуют в молодой плазме крови, или обнаружим клетки, которые продлевают жизнь, и сможем их синтезировать и давать в качестве лекарства пожилым людям. Об этом замечательно рассказал Тони Висс-Корей (Tony Wyss-Coray). Сейчас проводят технические испытания использования плазмы молодых организмов для лечения болезни Альцгеймера. Посмотрим, что у них получится.

Жить долго


Ещё одна история связана с исследователем Обри ди Греем (Aubrey de Grey), он тоже выступал на Ted Talk. Обри рассказывал: «Некоторые люди говорят: „Ну, продлим мы жизнь на 20 лет, умрём не в 80, а в 100. Но это всё равно не очень утешительно. Можем ли мы рассчитывать на что-то большее?“». Обри отвечал: «Да, можем». Why? Он приводит метафору со всемирным тяготением. Если возьмёте мяч и подкинете его, то он упадёт. Если подкинете его сильно, то он упадёт чуть позже. Но если вы подкинете его так, что он достигнет первой космической скорости, то мяч улетит в космос и больше никогда не вернется на Землю. «Смотрите, научно-технический прогресс развивается всё быстрее и быстрее, и, может быть, за те 20 лет, что вы ещё проживёте, придумают препарат, который продлевает жизнь ещё на 25 лет, а за эти 25 лет придумают препарат, который продлевает жизнь ещё на 30 лет, и так далее. И может быть, начиная с определённого возраста некоторые люди смогут прожить очень долго, тысячи лет». Многие учёные относятся к этому скептически. Но нет никаких серьёзных аргументов, почему это в принципе невозможно.

Мы видим, что научно-технический прогресс продлевает жизнь людям, причём по всей планете, во всех странах, даже в самых бедных, и продолжительность жизни стабильно растёт. А это значит, что ради продления жизни нужно развивать науку.

Напоследок хочу порекомендовать замечательный сайт geroprotectors.org — там собраны публикации о результатах исследований разных веществ с точки зрения продления жизни подопытным животным организмам.

Источник: geektimes.ru/company/mailru/blog/277096/