Epigenetic clock
How do I find out the age of the organs?
Vadim Gladyshev, Post-science
When we see a person, in most cases we can determine quite accurately how old he is. But sometimes a person doesn't look his age. One possible reason is due to the fact that a person's skin can age faster or slower than other organs. But perhaps aging itself happens differently in different people. What, then, is considered a universal age? Says biologist Vadim Gladyshev.
Biological age of the organism
If scientists have the opportunity to determine the biological age of an organism (real age) based on accumulated damage, and not chronologically, they will be able to study the aging of different organs. Thanks to such mechanisms, it would be possible to check to what extent interventions that affect life expectancy have an impact on biological age.
Until recently, there were no biomarkers that would allow such studies to be conducted. Scientists have tried many options, but in the end it became clear that oxidative damage, telomere length or protein aggregates – all these characteristics do not reflect the biological age of the organism.
Everything changed in 2011, when a scientist from Los Angeles, Steve Horvath, realized that DNA methylation could be used to determine biological age. He chose this method because one of the four DNA nucleotides can be methylated – cytosine. This is a relatively stable modification, and there are many millions of such places in the genome. If we analyze all the places where methylation occurs, it can be argued that there are some cytosines in the genome whose methylation with age reflects biological age. One separate place where this process takes place does not accurately reflect the age, but if you create a mathematical model in which there will be several hundred such places, each with a certain weight in the model, it will help to determine the biological age relatively accurately.
Epigenetic clock
In 2013, Steve Horvath published a paper that quickly became a classic, where he proposed the idea of an epigenetic clock based on DNA methylation, reflecting the biological age of an organism regardless of tissues. In the process of writing the article, the idea of such a watch seemed incredible, so many did not believe Steve Horvat. Over time, it became clear that such a model is gradually improving and better describes the aging process itself. There were clocks based on different individual organs – for example, a "clock" for blood, a "clock" for the liver, for other tissues, and a general clock. The phrase "Horvath's watch" has already become a household name.
Steve Horvath's ideas were studied and developed by other scientists, and it turned out that it was possible to build a clock not only for chronological age, as it was done at the very beginning, but also for other characteristics. It is known that harmful phenotypic changes accumulate with age, which can also be used to build a clock. As a result, there was a clock called PhenoAge – a phenotypic clock.
You can build a clock on mortality without considering the exact age of the organism, but concentrating on the remaining years of life. So there was an idea GrimAge, which Steve Horvath wrote about in a separate text published last year. All these clocks partially overlap with each other, but reflect different biology, so they give different information about different aspects of aging.
Fabric watches and rejuvenation effects
In our laboratory, we used the idea of such a clock on mice, because mice are a good model organism where you can test different interventions and study the mechanisms of aging. We have created a clock that predicts age regardless of the tissue of mice.
Besides, we have a blood clock. If mice limit the amount of calories consumed, then these mice will be younger by the blood clock than their chronological age shows. It has long been known that calorie restriction increases life expectancy, but according to the clock, this process also slows down aging.
Another situation is related to the shutdown of the growth hormone receptor. If you specifically cut off this gene, the mice will age more slowly. Or if adult cells are reprogrammed into embryonic cells through Yamanaki factors, then according to our clock, the age of these cells will be reset to zero. In addition to our laboratory, other researchers have published watches. Now there are about six different epigenetic clocks on mice, which have been built so far only for chronological age.
The idea and development of epigenetic clocks have opened up a new field of aging biology. Many of the questions that scientists are trying to answer now have not even been studied for several years. Now it is possible to check at what rate different organs age, to study when aging begins and what the dynamics of aging are in different organs, how the aging of one organ affects the aging of another organ, how it is possible to integrate all these processes to make a single model of aging. All these are completely new directions that have been studied only in recent years.
Steve Horvath has written over a hundred articles. Five years ago, he realized that people with Down syndrome age faster and look older than their chronological age. People who are obese also age faster, as do those infected with AIDS. Horvath was also one of the first to notice that the cerebellum ages more slowly than other parts of the brain.
Now this area of research has grown very much. Whole conferences are held on these topics. Research in this area of epigenetics is very important, because such watches can now be used in clinical trials, when doctors test interventions that increase life expectancy. With the help of epigenetic studies, it is possible to study the rejuvenation of the body and many other fundamental processes.
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