Life expectancy and sirtuin 6

Long Life gene helps repair DNA

Kirill Stasevich, "Science and Life" (nkj.ru )

There are a number of genes that affect important processes in the body and on which depends how long the body will live. One of them is the SIRT6 gene encoding the sirtuin 6 protein. It helps to correct damage in DNA – double breaks in chains and substitutions in genetic letters–nucleotides.

DNA damage happens all the time, and not only because of the harmful effects of the environment, our bad habits, but also because of completely ordinary biochemical reactions, in which, as it happens, dangerous by-products are obtained. For example, obtaining energy in a cell is associated with the appearance of powerful oxidants – oxygen radicals, which spoil both nucleic acids, proteins, and lipids.

Every cell has ways to neutralize dangerous substances and correct mutations in DNA. But with age, repairing proteins stop coping with mutations, and there are more and more of them. The cell gradually becomes decrepit and dies (if it does not degenerate into a malignant one). Biologists have long understood that life expectancy depends largely on how well DNA repair systems continue to work. And the fact that SIRT6 is one of the main players here, in fact, has also been known for a relatively long time. There were experiments when SIRT6 was turned off in mice, and the animals aged faster as a result. On the other hand, if several additional copies of SIRT6 were added to the genome of mice, the mice aged more slowly than usual.

Andrey Seluanov, Vera Gorbunova and their colleagues from Researchers at the University of Rochester, who study the biological mechanisms of longevity, have found another proof that sirtuin 6 largely determines life expectancy. The researchers compared how DNA repair occurs in 18 rodent species, from short-lived mice to centenarians like beavers and the aforementioned naked diggers, who can live for more than thirty years. Indeed, in species with a long lifespan, DNA repair – namely, the patching of double breaks in it – was much more effective.

But the difference in the effectiveness of DNA repair corresponded to changes in SIRT6: an article in Cell (Tian et al., SIRT6 Is Responsible for More Efficient DNA Double-Strand Break Repair in Long-Lived Species) states that sirtuin 6 worked more efficiently in beavers than in mice. The authors of the work traced the evolutionary changes in sirtuin and found that changes in the activity of sirtuin from species to species were associated with changes in five amino acids. At the same time, the increasing life expectancy, at least in rodents, was associated precisely with the repair of double-stranded breaks. The difference in the mouse and beaver variants of the SIRT6 gene was shown in experiments with human cells and fruit flies: with beaver sirtuin 6, cells coped better with DNA damage, and flies with it lived longer than with the mouse variant.

Now it would be interesting to compare the human sirtuin and the sirtuin of some animals that live much longer than us (for example, the Greenland shark). If the connection of the SIRT6 gene with life expectancy is confirmed again, it will be possible to think about how to optimize its work in older people – so that it functions like in long-lived animals. (Although you should not forget about other genes here.)

There are several sirtuin proteins, and other members of this family are also being studied for their connection with life expectancy. For example, sirtuin 1 is often talked about in connection with red wine: there was evidence that the substance resveratrol, which is especially abundant in red wine, somehow successfully acts on sirtuin 1, on which some immune processes and metabolism depend. However, it is worth saying that the data on the benefits of resveratrol remain largely controversial.

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