Molecule of eternal youth 28.05.2015

We hear so often about discovering a memory protein, or a gene for eternal youth, or a molecule that kills cancer cells on the spot, that it may seem that in the very near future we will have a long healthy life - for everyone. However, the progress of mankind, driven by science, is still developing more slowly than we expect from it. One of the reasons for high expectations is that the shadow side of experimental research rarely appears in popular scientific texts: all sorts of refinements and refutations of the results that other laboratories wanted to double-check. Figuratively speaking, the general public does not hear the rumble and crackle of collapsing hypotheses and theories.

A typical example is the recent history of a protein called tissue differentiation factor 11 (GDF-11). Not so long ago, he became another molecular "apple of rejuvenation": experiments have shown that he can reverse some age-related changes. We discovered this in an amazing experience when they combined the circulatory system of two mice, young and old. It turned out that young blood has a beneficial effect on the heart muscle. With age, the walls of the heart thicken, which has a bad effect on its work, and young blood, on the contrary, made the walls of the heart muscle thinner. When they tried to find out what kind of molecules could play a role here, they found 13 potential candidates, and among them - GDF-11. They checked it - and it turned out that it in itself has a rejuvenating effect on the heart muscle.

In addition, GDF-11 stimulated neurogenesis and vascular development in the brains of old mice, and also contributed to the restoration of the functionality of normal skeletal muscles. The data obtained confused many, since the picture turned out to be extremely contradictory. On the one hand, it was known that GDF-11 is high in young animals and very low in old ones. On the other hand, for a long time, only the fact that it controls the formation of olfactory receptors and receptors in the spinal cord was known about its functions. And, finally, most importantly, back in 2009, David Glass (David Glass), along with colleagues from the Institute for Biomedical Research, found that the same GDF-11 inhibits muscle growth. Then they were not surprised at this - since it is similar to the myostatin protein, which inhibits muscle differentiation, they expected about the same from GDF-11. I had to be surprised later, when it turned out that in other people's experiments it shows absolutely opposite properties.

And then the properties of GDF-11 decided to double-check again. The first thing we managed to find out was that until now it has been analyzed by a not too specific method: firstly, it has two forms, monomeric and dimeric (when two molecules are combined into one functional module), and secondly, as it was said, it similar to myostatin. The immunological method used earlier did not distinguish GDF-11 monomers from dimers (and the "sticking" of their molecules together can affect the functions of proteins quite strongly), and sometimes myostatin was also seized. By developing a more accurate method of analysis, the researchers tested how protein levels change with age. In mice, its level was generally too low to be reliable, but in rats and humans it was quite high - and it turned out that with age, the amount of GDF-11 certainly does not decrease, but even increases. When it was administered to old animals, no muscle regeneration occurred. Moreover, the muscles even recovered more slowly after damage - which is logical, if we accept that GDF-11 suppresses rather than stimulates regeneration. The full results of the experiments were published in the journal Cell Metabolism.

How can it be that the same molecule behaves so differently in different hands? The obvious answer is that some research group got the wrong results. But it is possible that both are right. So, Amy Wagers from Harvard, under whose leadership the work was done with young and old blood (after which everyone started talking about GDF-11 as a rejuvenation factor), says that it's all about different forms of protein, which - some of its forms still decrease with age. In addition, the Wagers group and the Glass group used different methods to damage the muscles: one by cardiotoxin, the other by extreme cooling. And it may well be that the regenerative effect of GDF-11 depends on the etiology of damage. Finally, in a certain sense, there is no contradiction between both works, since both they talk about the optimal level of protein required to maintain muscle functionality. It's just that some authors have shown that this level should not be lowered, while others - that this level should not be increased. And lastly, the rejuvenating effect of young blood may not necessarily take place only because of GDF-11; managed to count as many as 13 potential candidates for "rejuvenating apples".