CYTOR Upregulation Increases Muscle Function in Aged Mice

Researchers have in recent years identified CYTOR as a regulator of muscle growth, a line of work that is progressing towards the development of therapies to combat sarcopenia, the age-related loss of muscle mass and strength. This is a compensatory approach, forcing cells to override their natural response to the aged environment rather than trying to address the environment itself. Since evidence suggests that aged muscle stem cells are competent, capable of function, but made quiescent in response to the altered signaling environment in old tissues, restoring stem cell function (and thus muscle maintenance and growth) in this way may be at the more effective end of what is possible to achieve in the treatment of aging without targeting the deeper causes of dysfunction.

Your average 80-year-old has lost over 30 per cent of the muscle mass they had as a young adult. Without exercising to counteract the loss of muscle mass, humans already start to lose muscle around age 30. The body has two basic types of muscle fibres: the slow-twitch (type I) muscle fibres needed for endurance activities, and the fast-twitch (type II) muscle fibres used for short bursts of strength. As we age, we primarily lose type II muscle mass. "Our experiments show that CYTOR contributes to increased development of precisely the type II muscle fibres."

The next step for the researchers was to take a closer look at what happens when gene therapy is used to increase CYTOR levels. Using the CRISPR-Cas9 method, the researchers increased CYTOR production in live animals and in precursors to muscle cells from older humans. The results are very promising. "In human cells, CYTOR production increased as a result of gene therapy. We also observed that the therapy stimulated the cells to promote the development of fast-twitch type II muscle."

Experiments with mice confirmed that gene therapy not only provides a theoretical effect at the cellular level, but can actually provide improved muscle function. Gene therapy, which increased CYTOR production in the calf muscles of ageing mice, gave the mice increased muscle mass, better grip strength in their hind legs and greater running capacity. When the researchers reduced CYTOR production in young mice, however, the mice developed weaker muscles and more inflammation and cell death in the muscles. "The CYTOR gene seems to be absolutely crucial in order to maintain normal muscle function."


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