Muscle Changes in Aging Linked to a Fat Molecule

During aging, mice, like humans, become inactive and lose muscle mass and strength. A team of scientists has now discovered that when mice age, their muscles become packed with ceramides. Ceramides, known for their use in skin care products, are sphingolipids, a class of fat molecules that are not used to produce energy but rather perform different tasks in the cell.

The researchers found that, in aging, there is an overload of the protein SPT and others, all of which are needed to convert fatty acids and amino acids to ceramides.

The sphingolipids and ceramides are complex yet very interesting fat classes, and there is high potential to further study their role in aging, as they perform many diverse functions.

Next, the scientists wanted to see whether reducing ceramide overload could prevent age-related decline in muscle function. They treated old mice with ceramide blockers, such as myriocin and the synthetic blocker Takeda-2, and used adeno-associated viruses to block ceramide synthesis specifically in muscle.

Researchers Discover Ceramides Role in Aging Muscle Health

The ceramide blockers prevented loss of muscle mass during aging, made the mice stronger, and allowed them to run longer distances while improving their coordination.

To study this effect more deeply, the scientists measured every known gene product in the muscle using a technique called RNA sequencing. The findings were published in the journal Nature Aging.

It turned out that the blockade of ceramide production activates muscle stem cells, making muscles build up more protein and shifting fiber type towards fast-twitch glycolytic to produce larger and stronger muscles in aged mice.

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Finally, the scientists looked at whether reducing ceramides in muscle could also be beneficial in humans. They examined thousands of 70-80-year-old men and women from Helsinki and discovered that 25% of them have a particular form of a gene that reduces the gene products of sphingolipid production pathways in muscle.

The people who had this ceramide-reducing gene form were able to walk longer, be stronger, and were better able to stand up from a chair, indicating healthier aging, similar to mice treated with ceramide blockers.

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These findings are very important as they provide us with a strong incentive to develop inhibitors that could be tested in humans.



Source-Eurekalert