Researchers from the Nice Cancer and Aging Research Institute working on zebrafish, a species that ages in the same way as humans, have made an important discovery. By extending the lifespan of the cells of the intestine of this small vertebrate which is similar to us in many aspects, they have managed to rejuvenate its entire body by 40% ! A feat that confirms the thesis of an imminent Nobel Prize..
Living longer is not necessarily desirable if one is not in good health. This is why CNRS researchers at the Institute for Research on Cancer and Aging in Nice are working to understand the mechanisms of aging. Professor Miguel Godinho Ferreira and his teams are trying to find out if delaying this natural process is possible, without increasing the risk of cancer or disease. Their latest discovery puts one organ in particular at the heart of declining life : the gut.
The intestine, the organ through which aging begins
More than a century ago, the renowned Russian immunologist Elijah Metchnikov, winner of the 1908 Nobel Prize, found that aging resulted from increased inflammation of the intestine, due to the infiltration of microbes into the bloodstream. The older we get, the less the digestive tract plays its role of barrier and thus lets certain undesirable bacteria pass, which leads to faster aging of the body. The work published this May 4 in Nature Aging supports this theory.
"The intestine is the organ most exposed to the outside : it is in contact with food, the micro-organisms present in our environment that we ingest, our stress...", lists Miguel Godinho Ferreira, the main author of this study. "Of course, there is the skin too, but on the surface it is dead. The intestine is alive, and every five days most of its cells are renewed to keep the organ healthy. That's why little by little, it's getting older." This new research suggests that by slowing down the aging of the intestine, thanks to a new method, the whole organism would be rejuvenated. At least, in the animal model that these scientists used, the zebrafish.
The zebrafish, a vertebrate surprisingly close to us
This fish shares 70% of its genes with humans, and in particular the genes linked to diseases associated with age and cancer. Their way of aging is similar to ours. These scientists particularly worked on their telomeres. This is the end of the chromosomes, known to have a role in aging. The more our cells divide, and the older we get, the more these extremities get shorter. There is a way to keep them long: telomerase. It is an enzyme that we naturally secrete since we were born. By genetically modifying these zebrafish, by injecting this telomerase into their intestine, the researchers observed that the decline of this organ slowed down. Its wall remained watertight, retained its function as a protective barrier. Locally, the intestinal flora has also kept its variety, its balance. "Our results show that delaying the aging of intestinal cells in zebrafish also delayed the modification of the intestinal microbiota. This appears with aging, and is involved in various pathologies. This is also the case in humans", describes Mounir El Maï, researcher on aging and cancer who participated in the study.
Increase healthy life by 40%
But, more surprisingly : the aging of all the organs has slowed down ! The vertebrate organism kept its healthy condition for longer, without developing cancer, and remaining fertile (for males) later. which had never been observed before. "The fight against intestinal aging not only delays the aging of distant organs, but is sufficient to prolong the lifespan of mutant fish by 40%," the study states.
"You have to visualize a game of dominoes, adds Miguel Godinho Ferreira. If you drop one, does everything else fall too ? That was our hypothesis, and that's what happened. product. What is most spectacular is that thanks to this telomerase injected into the intestine, sterile animals have become fertile again." While the idea of the aging of the body could appear as a whole, a global situation, common to each organ, this study indicates something else. “Concerning aging, there is a hierarchy in the organs. And if we find it, we can reverse the process,” says its main author.
To a certain extent, could the regenerative power of youth that the intestine had in zebrafish be transposed to humans ? "The intestine, we talk about it as the second brain, but in reality, it is the first brain, because at the level of evolution, it appeared before", still tells us the researcher Mounir El Maï. "Showing that the aging of the whole organism could be initiated by the intestine is very interesting which could bring new therapeutic and diagnostic discoveries." Because telomeres also surely have a role to play in cancer and other immune or gastrointestinal diseases. The next step in his research will be to understand how all these organs communicate their signs of aging with each other.
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