Limitations of the study
muscle mass, sarcopenia, appendicular muscle mass
RECRUITMENT, SARCOPENIA
This analysis is limited by the size of the study populations and by the lack of a control group of individuals of similar age who did not have sarcopenia. Both these limitations arise from the samples coming from the LACE clinical trial. Firstly, the trial was placebo-controlled trial within the sarcopenia population, as a result there was no recruitment of individuals without sarcopenia. Secondly, recruitment of individuals to the trial proved difficult [Our analysis of total muscle mass is limited by being derived from bioimpedance rather than DXA. The bioimpedance was conducted as a screening tool to limit the number of DXA scans and the analysis of the DXA data was carried out to identify changes in appendicular muscle mass specifically. However, within our data set the bioimpedance measurements of total muscle mass are tightly correlated with the limb muscle measurements [(r = 0.815, p<0.001 arm and r = 0.830, p<0.001 leg muscle), associations that are similar to the association between arm and leg muscle measurements, both by DXA (r = 0.864, p<0.001 arm vs leg muscle)]. As we did not see any differences in muscle mass based on DXA measurements, it is unlikely that the lower reliability of the bioimpedance measurements affected the outcome.A further limitation is that, as a cross-sectional observational study, data demonstrate association only, and not causation. Indeed, it is not currently clear whether the changes in receptor mRNA observed in the GTEx are present in all tissues and are sufficient to significantly modify activin receptor signalling.