One of the consequences of the aging process is the loss of muscle mass and power –a condition known as sarcopenia–, and a study carried out by researchers at the Federal Polytechnic School of Lausanne (EPFL) in Switzerland, has found a new mechanism involved in the deterioration of muscles related to ageing: the accumulation of ceramides in them. The results of this work, which have been published in Nature aging, also reveal that reducing ceramides prevents the loss of muscle mass associated with age.
Ceramides are known to be used in skin care products. They are sphingolipids, a type of fat molecule that is not used for energy, but instead performs various tasks in the cell. “Sphingolipids and ceramides are a complex but very interesting class of fat, and there is great potential to further study their role in aging, as they perform many diverse functions,” says Dr. Pirkka-Pekka Laurila, lead author. study principal.
The EPFL scientists studied mice, since these animals, like people, become inactive and lose muscle mass and strength throughout their lives, and found that their muscles fill with ceramides as they age. They discovered, in particular, that during aging there is an overload of the SPT protein, among others, which are necessary to convert fatty acids and amino acids into ceramides.
Block ceramide to produce bigger, stronger muscles
They decided to see if reducing ceramide overload could prevent age-related decline in muscle function. They administered treatment with ceramide blockers, such as myriocin and the synthetic blocker Takeda-2, to elderly mice, and used adeno-associated viruses to block ceramide synthesis specifically in muscle. The ceramide blockers prevented the loss of muscle mass during aging, made the mice stronger, and allowed them to run longer distances while improving their coordination.
People with this form of the ceramide-reducing gene walked longer, were stronger, and were better able to get up from a chair, indicating healthier aging
To further analyze these effects, the researchers measured every known gene product in muscle using a technique called RNA sequencing. “It turned out that blocking ceramide production activates muscle stem cells, causing muscles to accumulate more protein and switch fiber type toward fast-twitch glycolytic fibers to produce bigger, stronger muscles in aged mice.” explained Dr. Martin Wohlwend, lead collaborator of the study.
Finally, they looked at whether lowering ceramides in muscle could be beneficial for people as well. To do this, they examined thousands of men and women who were between the ages of 70 and 80 and residing in Helsinki and found that 25% of them have a particular form of a gene that reduces the gene products of sphingolipid production pathways in muscle.
They found that people with this form of the ceramide-reducing gene walked longer, were stronger, and were able to get up from a chair better, indicating healthier aging, similar to that of mice that had been treated with ceramide blockers. ceramide. “These findings are very important, as they give us a strong incentive to develop inhibitors that could be tested in humans,” concluded Johan Auwerx, who led the EPFL team of scientists.
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