title: Telomeres shorten in response to oxidative stress in mouse skeletal muscle fibers.
abstract: Aging phenotypes are dictated by myriad cellular changes including telomere shortening. In most tissues, telomere shortening is accelerated during replication if unrepaired oxidative damage to telomere sequences is present. However, the effect of reactive oxygen species exposure on skeletal muscle telomeres is unknown. We sought to determine if oxidative stress shortens telomeres in isolated adult rodent skeletal muscle fibers. Flexor digitorum brevis muscles were dissected from male mice (C57BL/6, long telomere and CAST/Ei, wild-derived, short telomere) and dissociated into single fibers. Fibers were cultured at an oxygen tension of 2%-5% for 5 days in control, hydrogen peroxide (oxidant), or a combination of N-acetylcysteine (antioxidant) and oxidant containing media. Telomere length, telomerase enzyme activity, and protein content of TRF1 and TRF2 were subsequently measured. In both strains, oxidative stress resulted in significant telomere shortening in isolated skeletal muscle fibers, likely by different mechanisms. Telomerase activity was not altered by oxidative stress treatment but was significantly different between strains, with greater telomerase activity in long-telomere-bearing C57BL/6 mice. These results provide important insights into mechanisms by which oxidative stress could shorten skeletal muscle telomeres.
authors.affiliation: Department of Kinesiology, School of Public Health and.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Ludlow
authors.affiliation: Department of Kinesiology, School of Public Health and.
authors.forename: Espen E
authors.initials: EE
authors.lastname: Spangenburg
authors.affiliation: Department of Kinesiology, School of Public Health and.
authors.forename: Eva R
authors.initials: ER
authors.lastname: Chin
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park. Present address: Department of Food Science, Nutrition and Health Promotion, Mississippi State University.
authors.forename: Wen-Hsing
authors.initials: WH
authors.lastname: Cheng
authors.affiliation: Department of Kinesiology, School of Public Health and Sroth1@umd.edu.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Roth
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004249:DNA Damage; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013045:Species Specificity; D019098:Telomerase / Q000378:metabolism; D059506:Telomere Shortening / Q000187:drug effects / Q000235:genetics; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; C534796:TRF2 protein, mouse; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D006861:Hydrogen Peroxide; D019098:Telomerase
keywords: Low oxygen tissue culture; Oxidative stress.; Skeletal muscle fibers; Telomere length; Telomere-binding proteins