Molecular biologists from Yale uncovered the three-dimensional structure of the Klotho hormone that slows down aging, and found its unexpected connection with the real mechanism of cell rejuvenation, according to an article published in the journal Nature.
“We found out that Klotho does not actually protect the organs from aging directly, but only helps another FGF23 molecule to perform a similar function.This brings us closer to a true understanding of how the human body ages and allows us to create drugs that would block or strengthened the work of these hormones, “said Moosa Mohammadi of the University of New York, USA.
In recent years, scientists have discovered dozens of different hormones, proteins and other substances whose increase or decrease in concentration significantly prolongs the life of mice and other animals. A vivid example of this is the Klotho protein, whose high concentrations are observed in the body of long-lived humans.
This substance, as experiments on transgenic mice, whose DNA contains additional copies of the Klotho gene, have shown, significantly prolongs their life and at the same time slows down the aging of the brain, making them more intelligent in their advanced years of life. More recently, biologists have discovered that Klotho can “speed up” the work of the brain and young mice, which renewed the interest of the scientific community in this matter.
According to Mohammadi, the principles of Klotho’s work remained a mystery for molecular biologists, as scientists did not know what form this protein takes in the “fighting state” in the cells of the human body and in the bloodstream and with what other cellular systems it connects and interacts.
The only thing that scientists have learned over the past 20 years is that Klotho is somehow connected with hormones from the FGF family that are responsible for the growth of connective tissue. If the genes associated with Klotho or these signaling substances were removed, the life expectancy of the animals fell sharply, which indicated the joint nature of their action.
Mohammadi and his team checked whether this was really so, by freezing several Klotho molecules, FGF proteins and a number of other cell components with which they presumably react and enlightening them with a particle accelerator. These images of biologists were used to obtain an accurate three-dimensional model of all these proteins and to study how they can interact with each other and other parts of cells.
These models revealed an unexpected thing – it turned out that Klotho does not slow down aging by itself, this role is actually performed by another protein, FGF23. This hormone, as scientists say, is synthesized in the bone marrow and spreads to all other regions of the body, where it combines with Klotho and a number of other molecules and causes the cells to regenerate.
Using this information, as the biologist notes, you can create a molecule that will activate the molecules of FGF23 as well as Klotho, which will either slow the aging or suppress the work of this hormone if the body produces it too much, which often occurs with the development of kidney disease and hypertrophy of the heart.