Description
- Abstract:
- The mechanism of the muscle aging is a poorly understood subject. The senescence driven aging model is not readily applicable in the muscles, because mature muscle myofibers are post mitotic and not known to senesce. However, recent data suggests that some muscle myofibers do exhibit typical markers of senescence and there are mitotic muscle resident cell types that can still enter senescence with age. To see if there is any cell type in the skeletal muscles that enter senescence with age, we explored potential senescence markers that can be used in the muscles and identified p21 mRNA, p16 mRNA, and ORF1 protein of the LINE-1 retrotransposable element as the useful markers. We then utilized RNAscope HiPlex assay which is a hypersensitive RNA FISH technology that allows simultaneous visualization of multiple RNA targets, to identify different cell types in the mouse skeletal muscles. We combined the cell type specific markers with the aging markers to identify and characterize the aged cell types in the muscles. We report that some myofibers show increased expression of p21 mRNA with age. We also found presence of muscle resident cells expressing p16 mRNA. Finally, age associated increase in the ORF1 expression originated from the fibroadipogenic progenitors (FAPs) cells and some myofibers. We also found considerable ORF1 signals from an unknown cell type which requires the use of additional cell type markers. We propose the use of the RNAscope HiPlex in revealing the biology of the muscle aging by employing suitable cell type and aging markers. The spatial information preserved by this approach can complement the recent findings with the single cell sequencing.
- Notes:
- Thesis (Ph. D.)--Brown University, 2024
Citation
Seo, Jiwon,
"Identification of Aged Cell Types in Mouse Skeletal Muscles"
(2024).
Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:9eb783wk/
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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations
Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department....