Resilience of the mitochondrial reticulum in aging.

Abstract

Resting and maximal exercise respiratory rates (V̇o₂) 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. In addition, older skeletal muscle exhibited subtle yet significant reductions in the expression of proteins functionally related to substrate uptake and oxidation (mMCT1, mPC1, CPT1b, and HADH). Although there were no differences in mitochondrial contents per mg of muscle in older mice, there were significant losses of muscle, and hence, mitochondrial mass and proteins associated with membrane dynamics (Drp1, Fis1, and Mfn2). Furthermore, two-dimensional and three-dimensional, 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 reticulum.NEW & NOTEWORTHY We interrogated numerous structural and functional aspects of the mitochondrial reticulum using a standard mouse model of aging. We observed no age-associated changes in the coupling efficiency of mitochondrial preparations, but respiratory control decreased, and there were numerous subtle changes in mitochondrial morphology in aging mouse muscles. Overall mitochondrial functioning is well preserved in aging, indicating the performance decrements are related to loss of muscle mass and cardiovascular function.