Fitness in Humans Acts to Reduce Inflammation, But Does Not Reduce the Burden of Cellular Senescence in Muscle Tissue

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.



Perhaps corresponding to fact that most of us are pretty good at guessing someone's age, however fit they may be. iow, 80 year olds may be more or less fit/healthy looking, but they still have a similar senescent cell burden, dominating their appearance (skin, hair, circulation, etc.). (btw, I wouldn't say exercise is "free", since it's both time-consuming and potentially injurious, as well as often painful/stressful in advanced age, however necessary it may be [at this time] to moderate the effects of aging.)

Posted by: dtkamp at July 31st, 2020 9:04 AM

Thank you dtkamp. Your comment is consistent with my thinking, of why we don't necessarily need studies that measure lifespan and healthspan, and possibly don't need to find biomarkers that serve as proxies for those measures either. Instead, we need to measure the aesthetic aspects of aging.

Posted by: NY2LA at August 1st, 2020 11:31 PM

@ NY2LA That's an interesting view. Certainly the epigenetic age measures have turned out to be a mess. Am looking forward to OneSkin senolytics, and seeing a real difference in skin quality. (Does anyone know if they are still on track for a September release?) Have also been working up to trying Fisetin. (Any ideas on best source or methods of consumption?) Thx

Posted by: dtkamp at August 2nd, 2020 6:38 AM

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