Fitness produced by training is here shown to correlate with reduced inflammatory signaling, but has no effect on the burden of senescent cells in old muscle tissue. This is interesting, as the accumulation of senescent cells with age is responsible for a sizable fraction of inflammatory signaling in tissues. Senescent cells secrete a potent mix of signals that cause chronic inflammation and tissue dysfunction, and are an important contributing cause of aging. The likely explanation here is that the cellular adaptations to exercise act to reduce harmful aspects of persistent senescent cell signaling. There is a good deal of research to show that senescent cell signaling can be muted to various degrees. This is probably not as a good a strategy for the development of new therapies as is the targeted destruction of senescent cells, but exercise is free.

The aim of the present study was to determine if the training status decreases inflammation, slows down senescence and preserves telomeres health in skeletal muscle in older compared to younger subjects, with a specific focus on satellite cells. Analyses were conducted on skeletal muscle and cultured satellite cells from vastus lateralis biopsies (n=34) of male volunteers divided into four groups: young sedentary (YS), young trained cyclists (YT), old sedentary (OS) and old trained cyclists (OT). The senescence state and inflammatory profile were evaluated by telomere dysfunction-induced foci (TIF) quantification, senescence associated b-gal (SA-b-Gal) staining and qRT-PCR.

Independently of the endurance training status, TIF levels (+35%) and the percentage of SA-b-Gal positive cells (+30%) were higher in cultured satellite cells of older compared to younger subjects. p16 (4-5 fold) and p21 (2-fold) mRNA levels in skeletal muscle were higher with age but unchanged by the training status. Aging induced higher CD68 mRNA levels in human skeletal muscle (+102%). Independently of age, both trained groups had lower IL-8 mRNA levels (-70%) and tended to have lower TNF-alpha mRNA levels (-40%) compared with the sedentary subjects.

All together, we found that the endurance training status did not slow down senescence in skeletal muscle and satellite cells in older compared to younger subjects despite reduced inflammation in skeletal muscle. These findings highlight that the link between senescence and inflammation can be disrupted in skeletal muscle.