Senolytic Effects of High Intensity Exercise

Here find a study assessing whether or not high intensity exercise can have transient senolytic effects, at least based on using P16 as a marker of senescence. The effects seem to be transient, but the underlying biochemistry might be of interest for the production of more lasting senolytic therapies. As a caution, there is some thought that this marker can also represent non-senescent populations of macrophages. Given the role of these innate immune cells in the muscle tissue response to small-scale damage resulting from high intensity exercise, a part of the overall beneficial response, one might want to see other measures of the burden of cellular senescence in addition to P16.

Higher intensity exercise, despite causing more tissue damage, improved aging conditions. We previously observed decreased p16INK4a mRNA in human skeletal muscle after high-intensity interval exercise (HIIE), with no change following equivalent work in moderate-intensity continuous exercise. This raises the question of whether the observed senolytic effect of exercise is mediated by inflammation, an immune response induced by muscle damage.

In this study, inflammation was blocked using a multiple dose of ibuprofen (total dose: 1200 mg), a commonly consumed nonsteroidal anti-inflammatory drug (NSAID), in a placebo-controlled, counterbalanced crossover trial. Twelve men aged 20-26 consumed ibuprofen or placebo before and after HIIE at 120% maximum aerobic power. Multiple muscle biopsies were taken for tissue analysis before and after HIIE. p16INK4a+ cells were located surrounding myofibers in muscle tissues. The maximum decrease in p16INK4a mRNA levels within muscle tissues occurred at 3 hours post-exercise (-82%), gradually recovering over the next 3-24 hours. A concurrent reduction pattern in CD11b mRNA (-87%) was also found within the same time frame. Ibuprofen treatment attenuated the post-exercise reduction in both p16INK4a mRNA and CD11b mRNA.

The strong correlation between p16INK4a mRNA and CD11b mRNA in muscle tissues suggests a connection between the markers of tissue aging and pro-inflammatory myeloid differentiation. In conclusion, our results suggest that the senolytic effect of high-intensity exercise on human skeletal muscle is mediated by acute inflammation.


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