MyHC–SERCA mismatch as a marker of fiber-type remodeling in aging human skeletal muscle

Skeletal muscle fibers are commonly classified according to myosin heavy chain (MyHC) isoform, but fiber-type identity also involves coordinated expression of calcium-handling proteins such as sarco/endoplasmic reticulum calcium ATPases (SERCAs). Because fiber-type-associated proteins differ in turnover rate, incomplete remodeling may leave molecular traces of previous fiber identities. MyHC–SERCA mismatch may therefore provide insight into fiber-type remodeling, but its prevalence and morphology in aging human muscle are poorly defined. Vastus lateralis biopsies from young sedentary adults (Y-SED), older sedentary adults (O-SED) and older lifelong recreational exercisers (O-LLEX) were analyzed using immunofluorescence staining for MyHC-I, MyHC-IIa, SERCA1 and SERCA2 on serial sections. Fibers were classified as matched type I, type IIa or type IIx, or as MyHC–SERCA mismatched. Mismatched fibers were grouped into four categories, and fiber cross-sectional area and shape factor index were quantified. MyHC–SERCA mismatched fibers were present in all groups but were more prevalent in older adults than Y-SED. Mismatch did not follow a single staining pattern but comprised several distinct profiles. The most prevalent profile expressed type I MyHC with fast-type or dual SERCA expression. A smaller subset expressed type II MyHC with slow-type or dual SERCA expression and was less prevalent in O-LLEX than O-SED. In older adults, mismatched fibers showed heterogeneous morphology. Aging human skeletal muscle contains more MyHC–SERCA mismatched fibers than young muscle. These fibers show heterogeneous staining profiles and morphology. Lifelong recreational exercise was associated with fewer type II MyHC fibers expressing slow-type or dual SERCA. MyHC–SERCA mismatch may reflect different stages of incomplete fiber-type remodeling during aging.