Ceramides accumulate in aged muscle – Res
Researchers have revealed the accumulation of sphingolipids as a new mechanism affecting aging. Ceramides, the best-known class of sphingolipids, accumulate in aging muscle, impairing its function and affecting the functional capacity of older adults. These findings encourage researchers to develop potential drugs.
A study conducted at the University of Helsinki and the Swiss École Polytechnique Fédérale de Lausanne found that during aging, ceramides, a class of fat molecules called sphingolipids, begin to accumulate in the muscle, which weakens its function. Ceramides play an important role as a protective structure for the skin and are used in skin care products. However, their significance in aging has remained unclear so far.
With age, the amount of muscle tissue usually decreases and the ability to function decreases. In the current study, researchers found that the amount of ceramides and other sphingolipid molecules in muscle tissue increases as people age. Since sphingolipids act as intracellular messengers, this makes a difference.
“The link between sphingolipids and aging and related diseases is a vast and fascinating topic, as they mediate a variety of functions in cells, including cell division and differentiation and insulin signaling,” says Pirkka-Pekka LaurilaMD, from the University of Helsinki and École Polytechnique Fédérale de Lausanne.
The study was published in December Nature Aging diary.
Reducing ceramides increases muscle strength and stem cell function
Initially, the researchers investigated whether blocking ceramide production in cells could stop sarcopenia, or age-related muscle loss. They administered the drug myriocin, known to inhibit ceramide production, into the intraperitoneal cavity of aging mice. Myriocin slowed sarcopenia in mice, preserving their muscle strength and improving their balance and running ability. It was found that the effects were related to the function of muscle stem cells.
In general, the number of stem cells in muscles decreases with age. “We found that when the production of ceramide was inhibited, the number of muscle stem cells and their functional capacity were preserved better,” says the professor. Johan Auwerx from École Polytechnique Fédérale de Lausanne.
In the mice that received myriosin, the stem cells differentiated more efficiently into mature muscle fibers, which increases the number of white muscle fibers that maintain muscle strength and speed.
A significant role in human aging as well
Finally, the researchers wanted to find out if blocking ceramide synthesis could also prevent muscle loss in humans. They used thousands of samples collected from Helsinki residents aged 70-80 in the extensive Helsinki Birth Cohort Study. The researchers found that 25 percent of the subjects had a gene variant that had the same effect as myriocin, reducing the production of ceramides in the muscle.
“These older adults, who have a genetic mechanism that reduces ceramide synthesis in muscle tissue, were more fit for their age, as reflected by increased handgrip strength and the ability to walk long distances and get up from a chair. This leads to the conclusion that a drug that inhibits sphingolipid production might be worth testing in humans, says Professors. Jari Lahti from the University of Helsinki, which was involved in the Helsinki Birth Cohort Study led by the professor Johan Eriksson.
The study opens a new line of research on the effect of ceramides and other sphingolipids on aging and encourages the development of possible sphingolipid therapeutic strategies in humans as well.
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