Abstract
BACKGROUND: The potential impacts of drug-induced modulation of mitochondrial function in humans remain unclear despite the high prevalence of "mito-modulatory" medication use among older adults. Although these medications, such as statins and metformin, have undergone extensive characterization of their effects on mitochondrial function in vitro, the effects in humans are far more complex and poorly understood. METHODS: This study uses data from the Study of Muscle, Mobility, and Aging (SOMMA) to evaluate how mito-modulatory medication use is related to skeletal muscle bioenergetic capacity, measured by ex vivo high-resolution respirometry and in vivo phosphorus magnetic resonance spectroscopy in healthy older adults. RESULTS: We found that mito-modulatory medication use was related to lower maximal complex I & II supported oxidative phosphorylation (Max OXPHOS), maximal electron transfer system capacity (Max ETS), and maximal ATP production capacity (ATP Max) in men, but not in women. We also found this to be dependent on the number of medications used, in which higher mito-modulatory medication load was associated with lower Max OXPHOS, Max ETS, and ATP Max. CONCLUSIONS: Our results provide greater insight into the potential clinical effects of mito-modulatory medication use and highlight the need to test the impact of these medications on mitochondrial function in randomized trials.