S1_Figure.pdf

Resting and maximal exercise respiratory rates (O₂) decline in aging. Those losses have been attributed to impaired mitochondrial function, but the data are inconsistent with healthy aging. To interrogate the hypothesis of mitochondrial dysregulation in aging, we studied hind limb skeletal muscles from young and older, male and female, NIA C57BL/6JN mice. We observed no age-associated changes in coupling efficiency (ADP:O) of mitochondrial reticulum preparations, but respiratory control (RCR) was decreased in older mice. Additionally, older skeletal muscle exhibited subtle yet significant reductions in the expression of proteins functionally related to substrate uptake and oxidation (mMCT1, mPC1, CPT1b, HADH). While there were no differences in mitochondrial contents per mg of muscle in older mice, there were significant losses of muscle, and hence mitochondrial mass as well as proteins associated with membrane dynamics (DRP1, FIS1, and MFN2). Further, 2D and 3D, cross- and longitudinal muscle sections showed alterations in mitochondrial reticulum organization in muscles of older mice. Therefore, aging is associated with subtle, but significant changes in the organization and functioning of muscle mitochondrial reticula<b>.</b>