2024-01-15 14:00:00
Live longer and healthier. A dream cherished by most men.
A reality perhaps tomorrow thanks to the work carried out by Pascal Thérond and his team from the Valrose Institute of Biology (iBV) at the University of the Côte d’Azur. Nice scientists, following nearly eight years of research, have succeeded in providing proof of the determining role of a protein, called Hedgehog., – highly conserved across species – in longevity. A major discovery published in an excellent scientific journal (1).
“We have known for a long time that Hedgehog plays an essential role during embryonic development, as a tissue organizing molecule, introduces the researcher. When it is absent or mutated, major anomalies are observed: lack of development of the upper and lower limbs (in mice), Gorlin syndrome in humans (defect in division of the right and left hemispheres of the brain), individuals with only one eye; the cyclopia described by Homer, centuries BC, might thus be associated with mutations of this molecule.”
20% extra life
Among the questions that remained around this protein, one in particular tormented the Nice researcher: “Why is it still present in adult individuals, when it no longer has a function at this stage, or at least was supposed to no longer have one?” To try to resolve the enigma, Pascal Thérond and his team will genetically modify fruit flies or vinegar flies, animal models well known to research laboratories. “We have programmed them so that once they become adults, they no longer express this molecule.” And they will then make a first important observation: “These Hedgehog mutant animals have a life expectancy reduced by 78%!”
A first step towards discovering the essential role of Hedgehog in longevity. “But we needed to prove that by increasing its level during adult life, we obtained the opposite effect: an increase in lifespan.”
And this is what they will observe: “When fruit flies express high levels of Hedgehog, they live 20% longer than others.” A gain rarely obtained with genetic models, but also, above all, a “healthy” gain, as will be revealed by the “exercise tests” to which the animals will be subjected. “These “old” fruit flies are more mobile, more alert…”
And it is at the level of the brain that everything seems to happen, as the researchers will demonstrate: “Hedgehog targets specific cells, called glial cells, necessary for the proper functioning of neurons. Its absence affects in particular the network of neurons which produce dopamine, a neurotransmitter involved in the regulation of movements. It is then “sufficient” to reactivate the cells glial cells to restore longevity lost in mutants. »
Years of research in perspective
This molecule, via its action on glial cells, would in some way be one of the “conductors” of the overall functioning of the organism: at the cognitive, motor level… Abnormalities at its level would thus lead to a “cacophony “. “In his absence, it’s as if everything begins to malfunction… until it leads to premature death.”
Let us therefore cherish the hope that by targeting this new function of Hedgehog, which will have to be confirmed in other animals and in humans, we will one day be able to increase healthy life… Years of research in perspective for Nice team.
1. These studies published in Cell Reports earned Pascal Thérond the recipient in December 2023 of one of the most prestigious prizes of the Academy of Medicine, the Eloi Collery Prize.
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