Age related loss of muscle mass and function is a universal problem that affects everyone as we get older, beginning for many around the fourth decade of life. It contributes significantly to loss of independence, increased frailty and increasing health care costs. Our goal is to uncover key pathways involved in sarcopenia in the hope that we can provide new information that can be used to design effective interventions to delay or reduce muscle loss and weakness in the elderly. Studies in the Van Remmen laboratory aimed to uncover the underlying mechanisms of sarcopenia have been supported by a mouse model of increased oxidative stress caused by the lack of a key enzyme (CuZn-Superoxide dismutase (CuZnSOD)), which is responsible for the removal of the superoxide anion radical that is formed during normal aerobic respiration. Unchecked, superoxide anion can damage cellular organelles and pathways and lead to a number of pathologies. Among these are neuronal abnormalities and the accelerated deterioration of muscle mass (muscle fiber mass and number) and function (generation of force). Our more recent studies have probed the relative roles of muscle and neuronal oxidative stress and mitochondrial dysfunction on the initiation and progression of sarcopenia using a conditional knockout model for CuZnSOD that allows us to delete expression in specific tissues. Our studies have shown that the neuromuscular junction (NMJ) the specialized synapse that regulates the passage of nerve conduction to the muscle contraction is a critical link in maintenance of muscle mass and function. Finally, in related studies we are investigating similar pathways that regulate loss of muscle mass and function in Amyotrophic Lateral Sclerosis (ALS).