Predicting Myosin Heavy Chain Isoform Through Muscle Fiber Length in Older Adults

Abstract

Myosin heavy chain (MHC) isoforms directly impact muscle cellular contractile characteristics and are closely associated with other cellular functions (substrate metabolism, calcium handling, etc.). As such, MHC isoform has come to define muscle “fiber type” (MHC I = slow/oxidative and MHC II = fast/glycolytic). Due to the heterogeneity of MHC isoforms expressed within human skeletal muscle tissue, it is essential to determine MHC isoform to allow proper interpretation of tissue level outcomes that may arise from variations within or between fiber types. A priori estimation of fiber type would be a useful tool for ensuring even distribution of fiber type when considering cellular assays in which MHC isoform can only be determined after the fact. Based on the assumption that fibers of various MHC isoform would differently resist mechanical strain, we’ve demonstrated that MHC I fibers can be distinguished from MHC II fibers based on the ratio of fiber to bundle length (degree of stretch) during mechanical dissection. However, our approach used samples from healthy young adults and has not been tested in tissue from older adults, where cellular stiffness is likely elevated. Therefore, our objective is to test our ability to predict MHC isoform in older adults. We hypothesize that muscle fiber strain following dissection will predict MHC isoform in older adults. Methods: Muscle biopsies from the vastus lateralis muscle were obtained from two older adults (one male, one female). A total of 129 muscle fibers were dissected and measured. Fibers were then stored individually and MHC isoform was subsequently identified via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-Page). Receiver Operating Characteristics (ROC) and confusion matrix were used to assess the predictive capacity for fiber stretch on activation as an index of fiber type. Data: An ROC area under curve (AUC) of 0.634 which indicates that there is a relatively low predictive capacity. Summary: This study aimed to test the feasibility of an approach for predicting muscle fiber type through changes in fiber length upon mechanical dissection. Established in young adults, this study tested samples obtained from older adults to explore the potential effects of age. Preliminary data show that muscle fiber length can predict muscle fiber type in older adults, though the accuracy may be limited when compared with the same approach in younger adults. This lack of accuracy may be attributed to the increase in stiffness that occurs with age, limiting the capacity for strain and thus fiber type variability. A new threshold may need to be determined to increase the accuracy of fiber type prediction. Conclusion: Preliminary data shows that fiber length can provide a prediction for MHC isoform in older adults. NIH National Institute on Aging (1R21AG077125-01A1) and Achievement Rewards for College Scientists (ARCS) Oregon. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.