Skeletal muscle mitochondrial network dynamics in metabolic disorders and aging

Global demographics suggest an aging population, prompting concerns about an increase in the numbers of individuals with an age-associated loss of independence. Increasing adiposity is a risk factor for skeletal muscle insulin resistance, metabolic disease, and loss of skeletal muscle mass and function. Mitochondrial dynamics may be a therapeutic target for disorders of aging with an increasing number of studies suggest the presence of altered mitochondrial morphology in aging and obesity. Mitochondrial fragmentation is associated with metabolic disease development, while mitochondrial autophagy may be dysregulated in loss of muscle mass and strength. There remain significant gaps in the literature; however, the development of novel methodologies is facilitating a better understanding of mitochondrial network dynamics in age- and obesity- associated skeletal muscle dysfunction. With global demographics trending towards an aging population, the numbers of individuals with an age-associated loss of independence is increasing. A key contributing factor is loss of skeletal muscle mitochondrial, metabolic, and contractile function. Recent advances in imaging technologies have demonstrated the importance of mitochondrial morphology and dynamics in the pathogenesis of disease. In this review, we examine the evidence for altered mitochondrial dynamics as a mechanism in age and obesity-associated loss of skeletal muscle function, with a particular focus on the available human data. We highlight some of the areas where more data are needed to identify the specific mechanisms connecting mitochondrial morphology and skeletal muscle dysfunction. With global demographics trending towards an aging population, the numbers of individuals with an age-associated loss of independence is increasing. A key contributing factor is loss of skeletal muscle mitochondrial, metabolic, and contractile function. Recent advances in imaging technologies have demonstrated the importance of mitochondrial morphology and dynamics in the pathogenesis of disease. In this review, we examine the evidence for altered mitochondrial dynamics as a mechanism in age and obesity-associated loss of skeletal muscle function, with a particular focus on the available human data. We highlight some of the areas where more data are needed to identify the specific mechanisms connecting mitochondrial morphology and skeletal muscle dysfunction. programmed cell death. the process in which cellular contents are degraded by lysosomes or vacuoles and recycled. covers a variety of weight loss surgeries, including laparoscopic gastric banding surgery and Roux-en-Y gastric bypass (RYGB). a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass. a surgical procedure that involves the placement of an adjustable belt around the upper portion of the stomach using a laparoscope. The belt limits the expansion of the stomach conferring increased satiety in the patient. the deleterious effects of lipid accumulation in non-adipose tissue. the division of a single mitochondrion into two or more independent structures. the physical merging of the outer and then the inner mitochondrial membranes of two originally distinct mitochondria. thin double-membrane protrusions that connect the matrices of non-adjacent mitochondria. the selective degradation of mitochondria by autophagy. oxygen-containing radicals such as the superoxide anion (O2-), hydrogen peroxide (H2O2), and the hydroxyl radical (HO•) that can be generated by aerobic metabolism. ROS may serve as cell signaling molecules for normal biological processes; however, excessive production of ROS can result in damage to multiple cellular organelles and processes. a surgical procedure that involves the creation of a small gastric pouch connected to a roux limb, which bypasses a large portion of the small intestine. This results in the food bypassing the majority of the stomach, the duodenum, and the first 40–50 cm of jejunum. the age-associated loss of muscle mass and strength. a metabolic disorder that results in hyperglycemia due to reduced effectiveness of the hormone insulin (insulin resistance) an inability of the pancreas to produce enough insulin to overcome insulin resistance.