From the Neolithic to the early nineteenth century, the average human life span did not exceed 30 years. Even in the relatively recent 1940, life expectancy in the USSR was about 40 years, and in the most favorable countries of Scandinavia - 60 years. And only recently, thanks to the rapid development of medicine, people began to live as long as never before (they even thought about the massive transition beyond the 100-year mark).
But, alas, living long does not mean staying strong and healthy. And today, the majority of old people who have reached advanced years have suffered from chronic age-related diseases for decades, sometimes dreaming of leaving this mortal world as soon as possible.
Scientists are still looking for biological factors that lead to cell damage over time. Now researchers at Harvard University have discovered a link between aging and one of the main biological processes known as RNA splicing. This discovery not only sheds light on the role of the molecular mechanism in prolonging life, but also hints at the possibility of tuning it for healthy aging.
"What kills neurons in Alzheimer's is certainly different from the causes of cardiovascular disease, but aging is the main risk factor for all of these diseases," said senior study author William Mair. - Thus, one of the biggest questions - is there a general principle in the work of molecular systems that allows such diseases to gain a foothold in organs?
To understand how aging can be interfered with by RNA splicing, first it is worth recalling how protein molecules are synthesized, which are the main building blocks of cells in the human body, and also regulate the functioning of organs and tissues. The "recipes" for their manufacture are encoded in the genetic code and are stored in the nucleus of each cell, like in a library.
The creation of a new protein begins with the fact that on the basis of a separate section of DNA - a gene, the so-called messenger RNA is built, the amino acids encoded in the code are assembled into a protein.
But genes, like the RNA molecules built on their basis, contain non-coding regions that must be cut out during splicing before starting protein synthesis.
Stable production of RNA and proteins is key to staying young and healthy, so the researchers wanted to know what effect the changes in splicing that inevitably occur with age have.
Promotional video:
Mayr and his colleagues experimented with the ascaris worm Caenorhabditis elegans, which is a traditional and somewhat legendary model organism in biology. This is the first animal for which the genome has been decoded and a complete map of the neurons of the nervous system has been compiled. In addition, the roundworm may become the first living creature to travel to Mars in the near future. It is important that C. elegans has about the same number of genes as humans, so it is widely used in genetic research.
"Ascaris is an excellent subject for aging studies because these worms live for only three weeks, and during that time they show clear signs of age-related wilting," explains the study's first author Caroline Heintz. "For example, they lose muscle mass, their reproductive function decreases, their immune system deteriorates, and even wrinkles appear on their skin."
Since the worm cells are transparent, the scientists were able to tag individual genes with fluorescent proteins and observe in real time how the splicing process changes as the roundworm ages. Within five days, the team could not only identify individuals in the population in which splicing remained at normal levels longer than others, but also accurately predict the lifespan of each worm based on the dynamics of these changes.
“This is a really interesting result that suggests that someday we may be able to use splicing as a biomarker to detect early signs of aging,” Heinz says. But not only this made scientists happy, there was another important result.
Subsequently, the researchers developed a system of dietary restrictions, which, as shown by previous work, can prolong the life of worms (and not only). As a result, the process of splicing of roundworms constantly remained at the "youthful" level and did not change with age.
In the last step, the team focused on a separate element of the splicing process known as splicing factor 1 (SFA-1). It is part of the spliceosome, a massive molecular structure that is directly involved in the removal of non-coding regions of RNA. It turned out that an increase in the level of SFA-1 in cells prolongs the life of ascaris. This discovery is especially important because a similar element is present in the splicing mechanism in humans.
“These amazing results indicate that altered RNA splicing may be one of the main signs of the aging process,” says Mayr. "Our work opens up a whole new area of research that could help us understand how to extend life and stay healthy."
More information about the work of American scientists can be found in an article published in the journal Nature.
