A study has found that ceramides, a class of fat molecules called sphingolipids, start to accumulate in muscle during ageing, impairing function.
Researchers from the University of Helsinki and École Polytechnique Fédérale de Lausanne in Switzerland worked collaboratively on an investigation into the associations between ceramides and ageing.
The study was published in the journal Nature Aging.
Ceramides in the body increase with age
Ceramides act as a protective structure for the skin and are often used in skin care products. However, their association with ageing has so far remained unclear.
During ageing, people’s quantity of muscle tissue usually decreases, reducing functional capacity. In their study, the researchers found that the number of ceramides and other sphingolipid molecules in muscle tissue increase as people get older. This is important as sphingolipids serve as cells’ internal messengers.
“The link between sphingolipids and ageing and its related diseases is a broad and fascinating subject, as they mediate a range of tasks in cells, including cell division and differentiation as well as insulin signalling,” said Pirkka-Pekka Laurila, from the University of Helsinki.
Initially, the researchers investigated whether inhibiting ceramide production in cells stop sarcopenia, or muscle loss associated with ageing. The drug myriocin, which is known to inhibit the production of ceramides, was administered into the intraperitoneal cavity of ageing mice.
Myriocin can slow down sarcopenia
Myriocin did slow down sarcopenia in the mice, preserving their muscle strength and improving their balance and running capacity. The researchers believe the effects may be related to muscle stem cell function. The number of stem cells in muscles usually decreases as people get older.
“We found that when ceramide production was inhibited, the number of muscle stem cells and their functional capacity was better preserved,” said Professor Johan Auwerx from École Polytechnique Fédérale de Lausanne.
After receiving myriocin, stem cells in the mice were more effectively differentiated into mature muscle fibres. This increased the number of white muscle fibres responsible for maintaining muscle strength and speed.
The researchers also studied whether the inhibition of ceramide synthesis could prevent muscle loss in humans. The team examined thousands of samples collected from 70 to 80-year-old Helsinki residents in the Helsinki Birth Cohort Study. In total, 25% of the study subjects were found to have a gene variant that had the same effect as myriocin, reducing the production of ceramides in the muscle.
“These older adults with a genetic mechanism for reducing ceramide synthesis in muscle tissue were fitter for their age, as manifested by increased handgrip strength and ability to walk long distances and stand up from a chair. This leads us to the conclusion that a pharmaceutical inhibiting the production of sphingolipids could be worth testing in humans,” said Professor Jari Lahti from the University of Helsinki, who was involved in the Helsinki Birth Cohort Study.
The researchers believe the study could open up a new research line on the effect of ceramides and other sphingolipids in ageing. They hope their findings will accelerate the development of potential therapeutic strategies involving sphingolipids in humans.
