Concerns About Harms Caused by Senolytics are Not Supported by the Mouse Studies
Senescent cells accumulate with age to cause harm via their pro-inflammatory secretions. Senolytic therapies can selectively destroy these cells, to benefit the patient quite rapidly. Hypothesized harms that might be caused by senolytics generally revolve around the idea that some senescent cells might be structurally useful and hard to replace, so while having those senescent cells is bad, getting rid of them could be worse. The response to these concerns is to point to the mouse studies, in which no such problems appear to occur. The article here is a lengthy examination of this sort of argument of hypothetical concern versus actual mouse data in the specific case of muscle tissue.
Skeletal muscles are organized into long fibers composed of many nuclei, and when a fiber is damaged, the entire fiber is often lost. It seems that if any one of these nuclei were in a senescent state and were hit by a senolytic therapy, it might result in a fiber break and pull down the entire muscle fiber with it. And muscle fibers aren't easily replaced, and loss of muscle mass and function is already a major problem in aging, so the drug-induced destruction of muscle fibers could accelerate an aging person's slide into disability. Is this a real risk, and if so, does it make senolytic therapies a non-starter?
That's a worrying scenario for those of us who are excited by the promise of senolytic therapies. Fortunately, all the animal data refute it. When we get to the bottom-line question of what senolytic treatment did to the mass and function of muscle in old mice, we see good news all around. Not only did the senolytic-treated old mice not lose muscle, the treated animals actually sustained or restored the distribution of their muscle fiber sizes to the same distribution seen in young mice. Senolytic-treated mice also either gained more strength or suffered less age-related loss of strength than the untreated aging animals, leaving their muscle power partway between that of old and young untreated mice. And senolytic treatment also reduced the amount of dysfunctional repair activity in their muscles.
Link: https://www.sens.org/senolytics-muscle-cure-worse-than-disease/