Molecular biologists at Yale have uncovered the three-dimensional structure of the aging-slowing hormone Klotho and found it to be unexpectedly linked to the real mechanism of cell rejuvenation, according to an article published in the journal Nature.
“We found that Klotho does not actually protect organs from aging directly, but only helps another molecule, FGF23, 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 enhance the work of these hormones,”said Moosa Mohammadi from the University of New York (USA).
In recent years, scientists have discovered dozens of different hormones, proteins and other substances, increasing or decreasing the concentration of which significantly prolongs the life of mice and other animals. A striking example of this is the Klotho protein, which is found in high concentrations in the body of long-lived people.
This substance, as shown by experiments on transgenic mice, whose DNA contains additional copies of the Klotho gene, significantly prolongs their life and at the same time slows down the aging of the brain, making them more intelligent in their old years. More recently, biologists have discovered that Klotho can "speed up" the brain in young mice, which has renewed the scientific community's interest in this substance.
According to Mohammadi, the principles of Klotho's work remained a mystery to molecular biologists, since scientists did not know what form this protein takes in a "combat 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 managed to find out over the past 20 years is that Klotho is somehow linked to hormones from the FGF family, which are responsible for the growth of connective tissue. If the genes associated with Klotho or these signaling substances were removed, the life span of the animals dropped sharply, which indicated the joint nature of their action.
Mohammadi and his team tested whether this was actually the case by freezing several Klotho molecules, FGF proteins and a number of other cell components with which they supposedly react, and illuminating them with a particle accelerator. These images were used by biologists to create an accurate three-dimensional model of all these proteins and study how they might interact with each other and with 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 played by another protein, FGF23. This hormone, as noted by scientists, is synthesized in the bone marrow and spreads throughout the rest of the body, where it combines with Klotho and a number of other molecules and causes cells to regenerate.
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Using this information, as the biologist notes, it is possible to create a molecule that will activate the FGF23 molecules as well as Klotho, which will either slow down aging, or suppress the work of this hormone if the body produces too much of it, which often happens with the development of kidney disease and heart hypertrophy.