METFORMIN INGESTION PARTIALLY RESTORES AGE-RELATED IMPAIRMENT OF MYOGENIC POTENTIAL FROM MYOBLASTS ISOLATED FROM HUMAN DONORS
Z.S. Mahmassani, J.J. Petrocelli, A.I. McKenzie, N.M. de Hart, P.T. Reidy, M.J. Drummond
University of Utah, Salt Lake City, UT
Age-related impairments to myogenicity, or fusion potential, of myoblasts have negative implications for the ability of these cells to contribute to muscle repair after myofiber damage. This age-related deficit has been connected to impaired NAD biosynthesis; however RNA sequencing of muscle biopsies demonstrate insulin sensitizer Metformin, has the potential to alter NAD biosynthesis pathways. PURPOSE: Therefore, the purpose of this study was to determine if 2 weeks of Metformin ingestion improves the fusion potential of primary myoblasts isolated from muscle biopsies extracted from older adults and how this compares to young. METHODS: Muscle biopsies were extracted from young controls (<30yo; n=5) that did not receive metformin and from elderly subjects (60+yo; n=5) before and after 2 weeks of Metformin ingestion (2g/day). Primary myoblasts were isolated and expanded to passage 3 prior to experimentation. Cells were plated at equal densities between groups, and upon 95% confluence were differentiated in 2% serum for 8 days, in duplicate. Cells were stained for MyHC (MF20) and Nuclei (DAPI) and imaged at 10x magnification, in a 10x10 field of view mosaic (100 images), allowing for the capture of 10-20,000 nuclei per assessment. Co- occurrence of DAPI and MF20 were determined using the BioVoxxel Toolbox and Particle Analyzer (Image J) plugins. Fusion index was determined as [#DAPI co-occurring with MF20]/[Total #DAPI]*100. RESULTS: Fusion index of elderly subjects (27% ± 13SD) was significantly less (One Way ANOVA, P = 0.015, Old Pre vs Young: P=0.012, Tukey’s) than that of young subjects (61% ± 20SD), however Metformin partially rejuvenated this response (46% ± 9SD; Old Post vs Young: P=0.3, Tukey’s). CONCLUSION: The ability of Metformin to improve myogenicity of aged myoblasts provides valuable information on the “anti-aging” therapeutic effects of Metformin, as well as implications for regenerative medicine in geriatric populations.
Supported by ADA #1-19-ICTS-107 & by NIH Ruth L. Kirschstein NRSA 1T32HL139451.
Mahmassani, ZS; Petrocelli, JJ; McKenzie, AI; de Hart, NM; Reidy, PT; and Drummond, MJ
"METFORMIN INGESTION PARTIALLY RESTORES AGE-RELATED IMPAIRMENT OF MYOGENIC POTENTIAL FROM MYOBLASTS ISOLATED FROM HUMAN DONORS,"
International Journal of Exercise Science: Conference Proceedings: Vol. 8:
8, Article 38.
Available at: https://digitalcommons.wku.edu/ijesab/vol8/iss8/38