Alternatives to the death: how to defeat aging

As a modern molecular biology looks at the phenomenon of aging? Like trying to study aging, is there 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 reduction in age of 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 by about half. 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 overall worldwide noticeable progress.

More at the end of the XIX century it 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 a 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. The genome of the naked mole rat is already investigating scientists hoping to understand what makes it so special, and being long-lived.

If we assess the diversity of life on the planet, the mammalian life expectancy can differ by almost a hundred times, and animals in general - in the tens of thousands of times. With what it can be connected? It is obvious that an important role in aging and longevity genes play. What a shrew or vole from an evolutionary point of view, are not particularly interested in how to live a long time. In nature, few members of those 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 increased reproductive success. And the species, to get rid of the threat from predators, we're just seeing an increase in life expectancy. The same naked mole rat that lives under the ground, can live for 31 years. Another example of protection from predators - the ability to fly, as is the case with the bats and birds. But people can protect themselves with the help of science and technology.

There are organisms in which the gene has already laid the 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 octopus lays eggs, ceases to eat, and on average a month dies. This programmed death. But it turned out that this program can be undone, with surgically - just cut out a pair of glands, after which the octopus can not live a month, and 6-9 months.

There are examples of programmed cell death, when individual cells can kill themselves. This process is called apoptosis when cells accumulate a large number of mutations that do not become cancerous, does not pose a threat to the body, it is itself destroying, and quite reasonable - the cell is not just splashes all its contents out, and collapses into compartments, which can then be captured by neighbor cells and disposed of. 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." Wave may be induced artificially, e.g. freeze and unfreeze the worm. Also, scientists have found a way to stop this wave. The duration of the life of the worm does not increase, but if it is damaged, it will not die from. With the emergence of a wave starts the process of cell death, but then it's blue glow fades, and the worm continues to live on. Needless glow is just an indicator and it really is the wave of cell death along the intestine, which leads to death.

Why is this mechanism has arisen? Apparently, as a result of such a "death in an hour," the worm gets as food to their own offspring. Worms hatching babies die and become food for the next generation. Symbol of the sacrifice of motherhood.

In humans, at least in adults, such mechanisms were found. Our aging is an aggregate of many different processes. One of them - is the aging of cells.

Old cells can damage adjacent, can release substances that lead to inflammation. Older cells may become cancerous, so it would be good to get rid of them. The research results were recently published by the removal using a special medication old cells of a certain type in genetically modified rodents. And these rodents lived longer. That is quite possible to find an approach to aging cells.

The shortening of telomeres

human chromosome grayed telomeres - white

cell aging is associated with certain processes. One of them - a shortening of the telomeres. Way nature that with each 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 shorten from generation to generation, and they are old cells are very short. That is an old and a young man 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 a telomerase enzyme, 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. Experiments were performed in which virus delivered through a special telomerase in rodents, and telomeres were completed in 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 has been successfully tested

Similar experiments were 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 owns the largest biotechnology firm. 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 this story inspires many and says that telomere shortening is not an insurmountable problem of aging. damage accumulation

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 improperly working organelles like mitochondria damaged. At each cell division these injuries like are diluted, and each of the resulting two cells they should be twice smaller. That is, the active cell division could rejuvenate.

But the division has a dark side - cancer. There are genetic mutations that are not diluted. Cancer cell - cell has accumulated a large number of mutations that can lead to divide indefinitely, disabling of 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.

Starvation

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 chart of mortality:

Green color shows those who eat from the belly, blue spruce is 25% less, violet - 55% less, and red - 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 the green has died, the Reds are still alive. An impressive result. It turned out that the mechanism of prolonging life through starvation relevant to very different organisms, but not for everyone. There are those in which a partial deprivation reduces life expectancy. But in many species it works. 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 damage, these worms live about twice as long.

When DAF-2 receptor is activated, it triggers a cascade of cellular processes leading to protein inactivation, which is called the 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 meal is complete, everything is good, 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 broken, or if there is no food, it activates DAF-16, the cell thinks, "What a mess, I'm dying, stress, a nightmare! You need to save yourself "- and runs a bunch of defense mechanisms: by mutations of oxidative stress, heat shock, all in a row. Ie DAF-16 makes working hundreds of other genes that protect cells from various problems.

It turned out that a person has protein similar to DAF-16 and DAF-2. But similar to DAF-16 protein mutation was found. There are people with one variant of this protein, and there are people with another option. 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 the mechanisms of aging in humans.

Of course, not everything that we learn about the 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 yourself, your life is not extended.

body weight

Dwarf bats can live up to 40 years. Organisms with greater body weight live longer. But there are those whose life expectancy is much greater 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 also are 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". This genetic disorder that causes early appearance of signs of aging. At a young age there are senile diseases, and people on average live 13 years. For this disease causes a mutation in the gene that is 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 with aging nuclear matrix is ​​destroyed in the cells, and the slower it happens, the worms live longer. Perhaps the destruction of nuclear matrix plays an important role in human aging.

GH

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

In Yoda was flawed gene, which regulates the synthesis of growth hormone. He lived in the lab for four years - 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 than other people of the same region.

God TOR, the master of trash

Illustration: The Ban Lab

Our cells are able to remove himself from the debris 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 may contribute to rejuvenation of cells, but it prevents TOR protein.

What is he doing? He says: "Everything is useful. This stale sandwich that you have here is handy. It will be hungry, will block, and it 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 garbage accumulates and damages cells. Fortunately, there are substance-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. Rapamycin also prolongs the life of various organisms, such as mice, and quite strongly.

Rapamycin is very expensive, so in many cases use a much cheaper inhibitor of TOR - caffeine. Animal studies have confirmed that it improves and extends the life of autophagy. Also we have 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, this explains the consumption of resveratrol contained in red wine. Rodents the substance prolongs life. But then counted how much to consume wine man to resveratrol had the same effect - two barrels a day. Apparently, the French paradox soon connected with itself ethanol, which in certain low concentrations extended the life of nematodes. People who drink a glass of wine a day 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 how geroprotector ethanol - is a moot point. It arouses interest of scientists and metformin - a cure for diabetes. It has some side effects related to the gastrointestinal tract. There is research that confirms that metformin prolongs the life of worms.

But the longest - 50% - live nematodes due to alpha-ketoglutarate. He is remarkable that there is in people in large numbers, and has 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, incidentally, athletes use as a food additive to accelerate the growth of muscle mass. But there are conflicting reports whether it really helps in this.

Young Blood

Illustration: Popular Science

In one study, researchers surgically joined bodies of two rodent - old and young, combining their blood system. Under these conditions, old rodent living longer and young - less, while in older rodents increases the plasticity of the nervous system, ie the ability of nerve cells to form new neural connections. They even improves the regeneration of muscle tissue. It is clear that no one offers to sew together seniors and young children to senior citizens live longer. But maybe we'll find some factors that are present in young serum, or find cells that prolong life and can synthesize them and give as a medicine for older people. This wonderful told Tony Wyss-Korea (Tony Wyss-Coray). Currently conducting technical tests use plasma of young organisms for the treatment of Alzheimer's disease. Let's see what they come out.

To live a long time

Another story involves a researcher Aubrey de Gray (Aubrey de Grey), he also performed at the Ted Talk. Aubry said: "Some people say," Well, we will extend the life of 20 years, is not going to die in 80, and 100. But it still is not very comforting. Can we count on anything more? "". Aubrey answered, "Yes, we can." Why? He cites the metaphor of universal gravitation. If you will take the ball and throw at him, he will fall. If you throw at him much, it will fall later. But if you throw at it, so that it reaches the first cosmic velocity, then the ball will fly into space, never to return to Earth. "Look, scientific and technological progress is developing faster and faster, and, perhaps, for those 20 years, you still will live, will come up with a drug that prolongs life for another 25 years, and during these 25 years will come up with a drug that prolongs life for another 30 years, and so on. And maybe, since a certain age, some people can live for a long time, thousands of years. " Many scientists are skeptical. But there is no serious arguments why it is impossible in principle. We see that the scientific and technical progress extends the life of the people, with the whole world, in all countries, even the poorest, and life expectancy is growing steadily. This means that for the sake of prolonging life need to develop science.

Finally I would like to recommend a great site geroprotectors.org - there are collected the publication of the results of studies of various substances from the point of view of extending the life of an experimental animal organisms.