18 February 2019

The clock of aging

The main gear was found in the human biological clock

Only one group of genes was enough to determine the age

Polina Loseva, "The Attic"

For the past five years, the biological age of an organism has been determined using the "methylation clock" – a method that counts the number of sites in the genome that have undergone methylation. The longer an organism lives, the more such areas there are. Scientists from Massachusetts claim to have found the core of this clockwork mechanism – a group of genes that works so actively that age can be accurately determined by it alone.

The full text of the article by Meng Wang and Bernardo Lemos Ribosomal DNA harbors an evolutionarily conserved clock of biological aging will appear on the Genome Research website in six months – VM.

DNA methylation is the process of attaching inactivating labels, methyl groups, to a double helix. Because of them, a section of DNA is twisted and becomes inaccessible for reading information. This process occurs gradually, and with age, more and more genes are closed and stop working. This is the basis of the principle of the "methylation clock" – a method for determining the biological age by the number of methyl tags in certain parts of DNA.

The very first clock, invented by the American Steve Horvath, estimates the methylation of 353 sites in different regions of the genome. However, the compatriots of the Croat from Massachusetts offered a simpler method. They built their clocks by deciding to evaluate the methylation of only one group of genes encoding ribosomal RNA, and were thus able to correctly estimate age in mice, dogs and humans.

Ribosomal RNAs are part of the ribosome, which, in turn, is needed for the synthesis of all cellular proteins. Therefore, the genes encoding ribosomal RNAs always work in the cell – without them, the production of any proteins will stop. Since this region of the genome is so active, it can be assumed that it wears out faster than others. And indeed, a section of ribosomal DNA with a length of only 13 thousand base pairs was enough to determine the age.

A good marker of biological age has several criteria. Firstly, it should work on both humans and model organisms. The 353 sites identified by Horvath were very different in different mammals, and for each new species the clock had to be built anew. The new clock works at least in dogs, mice and humans, since ribosomal DNA is very conservative and almost does not differ even in such distant species.

Secondly, the marker should directly depend on the age. Horvath's clock relied on random sequences in different genes, which were obviously unrelated to each other and to the aging processes. At the same time, the new clock is based on a single DNA site that is directly related to age-related changes.

Finally, the marker should not only predict the age of the organism, but also respond to factors that slow down or accelerate the aging of the organism. The researchers confirmed that their new algorithm responds to calorie restriction, which is known to delay the biological aging of a variety of animals, and reprogramming cells that returns them to the stem state.

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