Longevity Briefs: Can Exercise Rid Your Muscles Of 'Zombie Cells'?

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

As we age, our tissues accumulate senescent cells. These ‘zombie cells’ are unable divide and don’t function properly, instead releasing harmful signalling molecules that turn nearby cells senescent. This is particularly problematic in skeletal muscle, as the accumulation of senescent cells contributes to a loss of regenerative capacity and the onset of sarcopenia, the age-related loss of muscle mass and strength. Skeletal muscle is also responsible for a large proportion of the body’s energy demands (even when not exercising), meaning that low skeletal muscle mass can contribute to obesity and type II diabetes.

Researchers are developing drugs designed to remove senescent cells, in the hope that these might be used to reverse age-related conditions like sarcopenia. However, it might be possible to reverse senescence through lifestyle modifications, without the aid of drugs. In this study, researchers investigate the effects of exercise on the presence of senescent cells in skeletal muscle.

The discovery:

Researchers recruited 55 participants and placed them into two groups:

23 young, lean individuals underwent a four-week supervised exercise program involving biking/running, circuit training, and warm-up/cool-down periods.
32 middle-aged, obese individuals underwent a six-month supervised exercise program combining strength and endurance training.

Muscle biopsies were taken from both groups before and after their respective exercise interventions. Both groups had significantly improved sensitivity to the blood sugar-lowering hormone insulin by the end of the study, which is not surprising and a known benefit of exercise. Both groups also showed significantly reduced markers of cellular senescence, with benefits being greater among the obese participants who underwent the longer exercise program.

Levels of three different senescence markers before and after the exercise program in lean (A-C) and obese (G-I) participants. The numbers above each graph are the p values (probability that results would have occurred due to chance). A p value of less than 0.05 is considered statistically significant.
Physical training reduces cell senescence and associated insulin resistance in skeletal muscle

Researchers also conducted cell culture experiments showing that cellular senescence in muscle cells is associated with impaired tissue regeneration and insulin signalling through reduced expression of certain key genes. They then found that salbutamol, an asthma drug that mimics some of the effects of exercise, was also able to reduce senescent cell markers in cell culture.

The implications:

This research provides evidence that the burden of senescent cells in muscle tissue is to some extent malleable, as it appears to be reduced by exercise. The exact mechanisms for this still need to be ironed out, but they are likely to be a combination of interconnected factors. The findings highlight the importance of regular physical activity for maintaining metabolic health and preventing sarcopenia.

While this study found exercise to have a greater impact in the middle-aged obese group than in the younger lean group, the exercise program for the obese group lasted a lot longer, so it’s not clear that they benefit more from exercise in terms of senescence (though it’s quite likely, since age and obesity are both associated with a higher burden of senescent cells). There’s not yet enough human evidence to say whether senescence-targeting drugs would be more effective than exercise for the removal of senescent cells, though animal studies suggest that this is likely.