Mediation analysis model
muscle mass
REGRESSION
We performed a mediation analysis to test the hypothesis that after adjusting for changes in muscle mass (leg lean mass), gene expression changes in muscle associated with CR compared to AL account for the changes in muscle strength. Of the original study population of 90 participants with 162 samples used for differential gene expression analysis, for this analysis we used data from 28 participants from the CR group and 16 participants from the AL group who had data at baseline and at least one follow‐up visit (of note, we originally had 17 participants for the AL group, but one participant with incomplete muscle mass data was excluded). As proxy measures of muscle mass, we calculated change in muscle mass (DeltaMass) between baseline and 24 months or baseline and 12 months if the 24‐month data were missing. Similarly, we calculated changes of muscle strength (DeltaStrength) for both average power and peak torque in isokinetic dynamometry at 60 and 180°sWe fitted a linear regression model for average change of muscle strength (DeltaStrength) controlling for change of muscle mass (DeltaMass) and sex, as follows (Equation For mediation analysis, we computed pathway‐specific scores as follows. First, for all leading genes of each pathway, we normalized log2(CPM) gene expression values (