Welcome to the MAD Lab!
Research interests & activity
Aging muscle is characterized by a progressive deterioration of both mass and contractile function. These changes lead to an increased risk of falls, impaired mobility, and physical frailty in the elderly. Amongst the most frequently implicated culprits in muscle aging are disturbances in the cellular powerhouses known as mitochondria. In this respect, recent work from our laboratory has shown that one of the most widely used methods for evaluating mitochondrial function in aging muscle, involving the mechanical isolation of mitochondria, destroys the mitochondrial reticular structure from that present in muscle fibers (see Video 1 and Video 2). Furthermore, these structural alterations are associated with disturbances in all of the major functions of the mitochondrion: respiration (to provide ATP), reactive oxygen species (ROS) emission (important to cell signaling and stress responses), and function of the apoptosis-regulating mitochondrial permeability transition pore (mPTP) (link). As such, it appears that mechanical isolation stresses the mitochondria, raising important questions about how we use and interpret data obtained with isolated organelles. Intriguingly, our recent work also shows that the severity of mitochondrial dysfunction in aging muscle is exaggerated when using isolated organelles (link). For these reasons, a major focus of our laboratory is to re-evaluate the magnitude of mitochondrial dysfunction and its relationship to atrophy in aging muscle, using cutting-edge mitochondrial functional assessment tools, and with a primary focus on studying the function of the mitochondrion in a preparation where all of the mitochondria are represented and where their reticular structure is intact: saponin-permeabilized myofibers. These studies will redefine our understanding of the involvement of the mitochondria in aging muscle, and will have important implications for understanding the role of the mitochondrion in aging itself.