| Autor: |
Mahmassani ZS; Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah., McKenzie AI; Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah., Petrocelli JJ; Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah., de Hart NM; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah., Reidy PT; Department of Kinesiology and Health, University of Miami Ohio, Oxford, Ohio., Fix DK; Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah., Ferrara PJ; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah., Funai K; Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah.; Molecular Medicine Program, University of Utah, Salt Lake City, Utah., Drummond MJ; Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah.; Molecular Medicine Program, University of Utah, Salt Lake City, Utah. |
| Abstrakt: |
Muscle progenitor cells (MPCs) in aged muscle exhibit impaired activation into proliferating myoblasts, thereby impairing fusion and changes in secreted factors. The antihyperglycemic drug metformin, currently studied as a candidate antiaging therapy, may have potential to promote function of aged MPCs. We evaluated the impact of 2 wk of metformin ingestion on primary myoblast function measured in vitro after being extracted from muscle biopsies of older adult participants. MPCs were isolated from muscle biopsies of community-dwelling older (4 male/4 female, ∼69 yr) adult participants before (pre) and after (post) the metformin ingestion period and studied in vitro. Cells were extracted from Young participants (4 male/4 female, ∼27 yr) to serve as a "youthful" comparator. MPCs from Old subjects had lower fusion index and myoblast-endothelial cell homing compared with Young, while Old MPCs, extracted after short-term metformin ingestion, performed better at both tasks. Transcriptomic analyses of Old MPCs (vs. Young) revealed decreased histone expression and increased myogenic pathway activity, yet this phenotype was partially restored by metformin. However, metformin ingestion exacerbated pathways related to inflammation signaling. Together, this study demonstrated that 2 wk of metformin ingestion induced persistent effects on Old MPCs that improved function in vitro and altered their transcriptional signature including histone and chromatin remodeling. |
