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Metformin treatment results in distinctive skeletal muscle mitochondrial remodeling in rats with different intrinsic aerobic capacities


Journal article


M. Bubak, A. Davidyan, Colleen L. O’Reilly, S. Mondal, Jordan Keast, Stephen M Doidge, Agnieszka K. Borowik, Michael E. Taylor, Evelina Voloviceva, Michael T. Kinter, S. Britton, L. G. Koch, Michael B. Stout, Tommy L. Lewis, Benjamin F. Miller
bioRxiv, 2024

Semantic Scholar DOI PubMed
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APA   Click to copy
Bubak, M., Davidyan, A., O’Reilly, C. L., Mondal, S., Keast, J., Doidge, S. M., … Miller, B. F. (2024). Metformin treatment results in distinctive skeletal muscle mitochondrial remodeling in rats with different intrinsic aerobic capacities. BioRxiv.


Chicago/Turabian   Click to copy
Bubak, M., A. Davidyan, Colleen L. O’Reilly, S. Mondal, Jordan Keast, Stephen M Doidge, Agnieszka K. Borowik, et al. “Metformin Treatment Results in Distinctive Skeletal Muscle Mitochondrial Remodeling in Rats with Different Intrinsic Aerobic Capacities.” bioRxiv (2024).


MLA   Click to copy
Bubak, M., et al. “Metformin Treatment Results in Distinctive Skeletal Muscle Mitochondrial Remodeling in Rats with Different Intrinsic Aerobic Capacities.” BioRxiv, 2024.


BibTeX   Click to copy

@article{m2024a,
  title = {Metformin treatment results in distinctive skeletal muscle mitochondrial remodeling in rats with different intrinsic aerobic capacities},
  year = {2024},
  journal = {bioRxiv},
  author = {Bubak, M. and Davidyan, A. and O’Reilly, Colleen L. and Mondal, S. and Keast, Jordan and Doidge, Stephen M and Borowik, Agnieszka K. and Taylor, Michael E. and Voloviceva, Evelina and Kinter, Michael T. and Britton, S. and Koch, L. G. and Stout, Michael B. and Lewis, Tommy L. and Miller, Benjamin F.}
}

Abstract

The rationale for the use of metformin as a treatment to slow aging was largely based on data collected from metabolically unhealthy individuals. For healthspan extension metformin will also be used in periods of good health. To understand potential context specificity of metformin treatment on skeletal muscle, we used a rat model (HCR/LCR) with a divide in intrinsic aerobic capacity. Outcomes of metformin treatment differed based on baseline intrinsic mitochondrial function, oxidative capacity of the muscle (gastroc vs soleus), and the mitochondrial population (IMF vs SS). Metformin caused lower ADP-stimulated respiration in LCRs, with less of a change in HCRs. However, a washout of metformin resulted in an unexpected doubling of respiratory capacity in HCRs. These improvements in respiratory capacity were accompanied by mitochondrial remodeling that included increases in protein synthesis and changes in morphology. Our findings raise questions about whether the positive findings of metformin treatment are broadly applicable.


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