title: Age-associated alterations of the neuromuscular junction.
abstract: Age-related loss of muscle mass and function greatly affects quality of life in the elderly population. Several hypotheses have been proposed but accumulating evidence point to alterations in neuromuscular system during aging as a key event that leads to functional denervation, muscle wasting, and weakness. Over the past few decades, age-associated degeneration of the neuromuscular junction (NMJ) and its components have been well documented. With advancing age, pre-terminal portions of motor axons exhibit regions of abnormal thinning, distension, and sprouting whereas postsynaptic endplates decrease in size and reduce in number, length, and density of postsynaptic folds. Although the exact underlying mechanisms are still lacking, recent studies provided direct evidence that age-associated increase in oxidative stress plays a crucial role in NMJ degeneration and progression of sarcopenia. Homozygous deletion of an important antioxidant enzyme, Cu,Zn superoxide dismutase (CuZnSOD, SOD1) leads to acceleration of age-dependent muscle atrophy, with a significant NMJ degeneration similar to that seen in old wild-type sarcopenic animals. In this short review, we briefly summarize the current understanding of some of the cellular and molecular changes in the NMJ during aging and suggest a role for oxidative stress and mitochondrial dysfunction in age-related changes in the maintenance of neuromuscular innervation.
authors.affiliation: Department of Cellular Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
authors.forename: Youngmok C
authors.initials: YC
authors.lastname: Jang
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009469:Neuromuscular Junction / Q000254:growth & development*; D018384:Oxidative Stress
chemical_list: D036341:Intercellular Signaling Peptides and Proteins