If we had lived for eight centuries
Scientists are closer to solving longevity
Alexey Ognev, RIA Novosti
This saber-toothed rodent has long been in the spotlight of scientists. They expect to borrow a recipe for longevity, eternal youth and good health from him. What have you learned about naked diggers lately — in the RIA Novosti material.
Deep Implementation Agent
For more than thirty years, Russian biologists have been exploring the unique wildlife of Ethiopia. More than seventy species of fauna have been described, of which fifteen are completely new to science. Having studied the inhabitants of forests and mountains, we started on deserts and semi-deserts. It is in this natural area in eastern Africa that the famous naked diggers (Heterocephalus glaber), small hairless rodents leading an underground lifestyle, are born.
They form colonies of tens and hundreds of individuals. At the head is the elite: the queen, producing offspring (in the picture), and two or three of her spouses. The majority of the population are workers deprived of family joys. They dig tunnels, get food, feed royal cubs, protect relatives. Such a community structure (eusocial) is inherent, for example, in ants and termites, but is absolutely not characteristic of mammals.
Naked diggers dig holes in a conveyor way: an advanced worker loosens the soil with incisors, the rest of the chain throw it back. The total length of the winding passages reaches several kilometers, and the area exceeds a football field.
It is not difficult to find these labyrinths — by mounds of freshly thrown soil. It is much more difficult to understand whether it is a residential colony or extinct, and to catch the animals themselves, says Leonid Lavrenchenko, head of the theriological detachment of the joint Russian-Ethiopian biological expedition, head of the Laboratory of Mammalian microevolution at the Severtsov Institute of Ecology and Evolution of the Russian Academy of Sciences.
"We learned to catch for a long time," says the scientist. — They came up with special live traps. They put their favorite delicacy there — freshly cut sweet potatoes. It tastes like frozen potatoes. And later the locals showed how to catch with almost bare hands. They often have fun like that. You just need to sit down near a fresh mound and make certain sounds — a bizarre combination of smacking and whistling. The animal will come by itself. I didn't believe it, but we tried — it works!"
The evolutionary fork
Naked diggers don't just live ten times longer than other rodents, but they don't age either. They have no external age signs, and elderly individuals do not die more often than young ones. In addition, they are extremely resistant to cancer and cardiovascular diseases. And the reproduction of the queen does not decrease over the years.
"They live longer than thirty years. It's amazing. It's as if you and I have lived for eight centuries. In addition, this animal, apparently, does not feel pain from thermal and chemical burns, is extremely resistant to high concentrations of carbon dioxide. They don't even need water. They feed on tubers of plants, eating them from the inside," says Lavrenchenko.
Genetic studies show that the naked digger separated from mice and rats 75 million years ago, from other members of the digger family — about 30 million. According to the biologist, the semi—deserts of the Horn of Africa are one of the oldest and climatically most stable landscape regions of the continent. That is, the species had the opportunity to calmly evolve in a stable climate and the depth of underground burrows that reliably protect against enemies. So the naked digger gradually acquired unique properties. An important role was also played by the feeding of giant underground tubers of Pyrenacantha malvolistnaya, which provides food even for huge colonies of rodents.
Their genome was decoded ten years ago in the hope of establishing the causes of longevity and resistance to cancer. We have really found out something, but for the completeness of the picture we need to study the full genetic diversity of the species. This will help to identify specific mutations responsible for unique properties, and will greatly help biomedicine.
"The founders of laboratory colonies in research organizations in different countries come from the same place in Southern Kenya. But the range of the species is quite large, and the question arises: how unique is characteristic of all naked diggers?" — Leonid Lavrenchenko notes.
Recently, Russian scientists were the first in the world to examine the evolution of naked diggers throughout their habitat and identified two markedly different lines: one in the eastern part of the range, the other in the southern (it is studied in laboratories).
"Our work is based on the analysis of eight genes: two mitochondrial and six nuclear. The fact is that in order to establish the degree of divergence between different lines, it is necessary to use an arbitrary set of a sufficiently large number of genes," explains Lavrenchenko.
The next step is to compare the complete genomes of the eastern and southern evolutionary lines. Then it will be clear whether these are subspecies or two different species.
Deadly skirmishes
"We have about two hundred naked diggers in our laboratory. Ten colonies, each with its own long-lived queen. When she weakens before giving birth, and this happens every three to four months, intrigues begin. Another female feels that her hour has struck and is trying to make a coup," says Vera Gorbunova from the University of Rochester (USA), a specialist in gerontology.
Male inseminators usually remain faithful to the queen, so the applicant has to look for another spouse. A civil war is breaking out.
"A lot of animals die in these battles. There can be three outcomes in nature: either the queen is killed, or her rival, or she leaves and creates a new colony. We in the laboratory prefer the third option. If we see that a coup is brewing, we immediately plant the troublemakers so that they establish their own kingdom," the interlocutor of RIA Novosti continues.
Naked diggers are more likely to die in a fight with their own kind or from an accident than to die of old age or be eaten. They are safely hidden from enemies in nature. This probably explains their longevity.
"In principle, life expectancy is determined by evolutionary expediency. For example, it is completely useless for a field mouse to live a hundred years, because a fox will eat it anyway in the first two years. It makes no sense for this kind of rodent to develop mechanisms of longevity, to invest energy in it. And now imagine an island where there are no foxes at all. After millions of years of natural selection, mice that live a long time will prevail. Naked diggers have a similar situation: they live underground and are protected from enemies. They have such exceptional health because it is justified for them," the gerontologist concludes.
While the clock is ticking
Scientists already understand quite well the molecular mechanisms that make naked diggers special. Gorbunova's research team found a very high content of hyaluronic acid in the skin and other connective tissues of these rodents, which protects against cancer and possibly other diseases. In addition, it turned out that they have very accurate protein synthesis (defects are 40 times less than in a mouse) and effective repair of damaged DNA.
This is confirmed by experiments: when certain genes of the naked digger were transplanted into mice, they began to live ten percent longer and get sick less often.
A recent scientific paper is devoted to an attempt to determine the aging rate of a naked digger. Behind the external and internal physiological signs there is a change in DNA, malfunctions in the functioning of its individual sections, a violation of the shape of the laying of the molecule. But not only that. Over time, methylation occurs in the body — the addition of a methyl group to cytosine, one of the nucleotides in DNA. Tracking of methyl tags allows you to establish the biological age. Scientists call this an epigenetic clock.
"Many colleagues thought that maybe this clock does not tick at all for a naked digger, because the probability of death does not increase with age," Vera Gorbunova outlines the problem.
It turned out that naked diggers still have epigenetic aging, although it is very slow. Moreover, queens age the slowest in the colony.
"The queen can give birth to 20 cubs at a time, this is a very big load for the body. One female has produced more than 900 cubs in 12 years. Such an increased reproductive function should accelerate aging, and the naked digger has the opposite. This is a paradox," the researcher emphasizes.
In other animals, epigenetic aging goes hand in hand with physiological aging, causing external changes, age-related pathologies. In naked diggers, these two processes are separated.
"DNA is stacked inside the cell nucleus in a certain order: some genes are open and actively working, others are closed. Epigenetic aging means that this order is disrupted with age, as a result, the cell functions worse. In the naked digger, we also see changes in methylation, and nevertheless the cells still work well. Perhaps the DNA stacking changes less. To be honest, it's hard to say how they achieve this," the biologist admits.
One of the assumptions is that this rodent species has learned to resist some factors of epigenetic aging. Earlier, Vera Gorbunova and colleagues showed that the cells of a naked digger react to radiation and carcinogenic proteins to a much lesser extent than human or mouse cells. DNA, of course, is damaged, but not as much as in other mammals.
The Elixir of eternal youth
The naked digger is not the only long—lived animal. For example, a porcupine lives for 20 years. This is advantageous from an evolutionary point of view, because needles protect it from enemies. Bats — 40. They are studied mainly in the wild, and detailed laboratory studies are still to be carried out.
But the real methuselahs among mammals are bowhead whales. Their age (there is evidence that it reaches two hundred years) is determined by the lens of the eye — an excellent biological chronometer. According to Vera Gorbunova, such an evolutionary result was obtained, among other things, due to the fact that they had almost no enemies before the whalers.
Whales, like naked diggers, rarely find cancer. These sea giants don't get sick much at all. But the molecular mechanisms of this phenomenon have yet to be studied.
By revealing the secret of the exceptional health of naked diggers, whales and other centenarians, scientists hope to help humans. For example, hyaluronic acid has long been used to treat joints and wounds. Now that they have learned that the naked digger has its high-molecular forms in its cells, new methods of therapy can be developed.
Researchers have identified molecules that slow down the breakdown of hyaluronic acid in tissues. In the future, this will help to create a cure for old age. It will be much more difficult to improve protein synthesis in humans, but there are already some considerations on this score.
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