H19X-encoded non-coding RNAs are associated with loss of muscle and old age in human: A quantitative histological study using the Genotype-Tissue Expression (GTEx) database

Loss of skeletal muscle mass and function is commonly seen in individuals with chronic illness, older age, and altered hormonal and/or endocrine functions. Whole-genome survey of human muscle biopsies has identified several miRNAs which are associated with chronic diseases and thus named “atromiRs.” Using murine models, we have showed that H10X-encoded atromiRs miR-424/miR-503 downregulates muscle mass by directly targeting protein translation initiation factors. We hypothesized that H19X-encoded non-coding RNAs (ncRNAs) are involved in the pathogenesis of muscle atrophy/wasting in humans, and the levels of the ncRNAs are correlated with the loss of skeletal muscle mass in old age. A total of 803 samples from the GTEx project, which contains both skeletal muscle RNA expression information and skeletal muscle biopsy images, were included in the study. The samples were further classified into eight groups based on the levels of miR-503HG (host gene of miR-424/miR-503) reported in the database. Quantification of histopathology in HE-stained muscle sections were manually performed in group 1 (n=89) and 8 (n=100), which had the lowest levels or highest levels of miR-424/miR-503, respectively. The degree of muscle atrophy, fibrosis, and interfascicular/perifascicular fat accumulation were assessed with a grading scale of 0-3. The total muscle histology score was also calculated as a sum of all three scores. Unpaired student t-tests were used to compare histological scores, BMI, and age between the two groups. All tests were two-tailed and p-values less than 0.05 were considered significant. There is no significant difference between the two groups in sex ( p= 0.55). In agreement with our recent study, high levels of miR-503HG (group 8) are associated with old age ( p= 0.02), and a trend of higher BM ( p= 0.07). Notably, high levels of miR-503HG are significantly correlated with muscle atrophy ( p= 0.001) and a total muscle wasting score ( p= 0.03) from histological assessment. These findings suggest the increased levels of H19X-encoded ncRNAs in human skeletal muscle are associated with muscle mass loss and potential sarcopenia. The results of our study may provide insight into the underlying role of H19X-encoded ncRNAs in the pathogenesis of geriatric muscle loss. The research was funded by the University of Houston internal fund to enhance and advance research (to YL). This is the full abstract presented at the American Physiology Summit 2023 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.