title: Intrinsic stiffness of extracellular matrix increases with age in skeletal muscles of mice.
abstract: Advanced age is associated with increases in muscle passive stiffness, but the contributors to the changes remain unclear. Our purpose was to determine the relative contributions of muscle fibers and extracellular matrix (ECM) to muscle passive stiffness in both adult and old animals. Passive mechanical properties were determined for isolated individual muscle fibers and bundles of muscle fibers that included their associated ECM, obtained from tibialis anterior muscles of adult (8-12 mo old) and old (28-30 mo old) mice. Maximum tangent moduli of individual muscle fibers from adult and old muscles were not different at any sarcomere length tested. In contrast, the moduli of bundles of fibers from old mice was more than twofold greater than that of fiber bundles from adult muscles at sarcomere lengths >2.5 μm. Because ECM mechanical behavior is determined by the composition and arrangement of its molecular constituents, we also examined the effect of aging on ECM collagen characteristics. With aging, muscle ECM hydroxyproline content increased twofold and advanced glycation end-product protein adducts increased threefold, whereas collagen fibril orientation and total ECM area were not different between muscles from adult and old mice. Taken together, these findings indicate that the ECM of tibialis anterior muscles from old mice has a higher modulus than the ECM of adult muscles, likely driven by an accumulation of densely packed extensively crosslinked collagen.
authors.affiliation: Biomedical Engineering, University of Michigan, Ann Arbor, Michigan;
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Wood
authors.affiliation: Biomedical Engineering, University of Michigan, Ann Arbor, Michigan;
authors.forename: Erdan
authors.initials: E
authors.lastname: Kayupov
authors.affiliation: Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan; Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan; and.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Gumucio
authors.affiliation: Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan; Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan; and.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Mendias
authors.affiliation: Biomedical Engineering, University of Michigan, Ann Arbor, Michigan; Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Claflin
authors.affiliation: Biomedical Engineering, University of Michigan, Ann Arbor, Michigan; Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan; svbrooks@umich.edu.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Brooks
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000502:physiology*; D012518:Sarcomeres / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D017127:Glycation End Products, Advanced; D003094:Collagen; D006909:Hydroxyproline
keywords: age crosslinking; collagen; muscle mechanics; passive tension; tangent modulus