Role of altered cortisol production in the development of sarcopenia

Skeletal muscle mass and function is decreased as we age, a condition known as sarcopenia. Ageing is associated with increases in minimum and mean cortisol plasma levels and shortening of the evening cortisol quiescent period, suggesting impaired circadian function and higher basal levels with increasing age (Stamou et al, 2023). It has also been shown that the deleterious effects of bed rest on human skeletal muscle are exacerbated by hypercortisolemia (Fitts et al, 2007).The aim of this study was to examine the direct effects of increasing levels of cortisol on muscle cells. C2C12 myoblasts were fused to myotubes by serum deprivation for up to 7 days. Cellular viability was assessed using light-microscopy to identify any gross changes in cell morphology at 3, 24 and 48 hours following treatment with a range of cortisol concentrations in the physiological range (10 – 0.1uM). Indices of muscle atrophy and evidence of altered levels of inflammatory cytokines was determined by mRNA analyses and release of cytokines/chemokines by myotubes was assessed using bead based multiplex technology (Luminex immunoassay).Cortisol treatment had no significant effect on C2C12 myotube viability at any concentration or time point, or on gene expression of IL-6, RANTES (CCL5) or MCP-1 (CCL2) compared with control untreated myotubes. No increase in the release of cytokines and chemokines from C2C12 myotubes was seen following treatment with cortisol and in some instances a significant decrease in cytokine/chemokine production was seen, particularly following treatment with higher concentrations of cortisol when compared with control values (eg, 10uM cortisol, 24 hours post-treatment: IL-6: 1.6 +/- 1.6% CXCL5: 17.4 +/- 1.8%; KC (CXCL1): 11.6 +/-10.3%. These data are in contrast to previous work from our group which revealed an increase in the release of IL-6, CXCL-1 (KC), CCL2 (MCP-1) and CCL5 (RANTES) from C2C12 myotubes following treatment of myotubes 25ng/ml TNF-α (Lightfoot et al, 2015).In summary, increased levels of cortisol do not appear to have any direct deleterious effects on myotube viability or production of pro-inflammatory cytokines. However, this does not exclude any indirect effects of cortisol on muscle including the effects on other organs indirectly affecting muscle function. It may also be that cortisol has a deleterious effect when muscle is under stressful conditions and this possibility will also be examined. Fitts et al (2007). doi: 10.1152/ajpcell.00573.2006 ; Lightfoot et al. (2015) doi: 10.1016/j.redox.2015.08.007 ; Stamou et al (2023) doi.org/10.1016/j.maturitas.2022.10.006 . The authors would like to thank the EU/BBSRC and CIMA for generous funding. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.