Muscle recovery was characterized by an enhanced collagen transcriptional profile and increased senescence‐associated secretory phenotype factors that were prevented with metformin
To further examine the underlying mechanisms of altered muscle remodeling programs in the metformin treated group during recovery from bed rest, we conducted RNA sequencing on muscle biopsy samples at PRE, POST, and REC. After bed rest, 441 gene transcripts changed in the placebo group (Figure Collagen transcriptional profiles and cellular senescence driving transcripts are reduced with metformin. After bed rest volcano plot displaying significantly up and downregulated transcripts in red with placebo (a) or metformin (b). After recovery volcano plot displaying significantly up and downregulated transcripts in red with placebo (c) or metformin (d), with collagen gene family members highlighted. (e–h) GSEA enrichment plots for Collagen Formation, Collagen Biosynthesis, and Modifying Enzymes, Assembly of Collagen Fibrils and Other Multimeric Structures, and TGF‐β Signaling pathways after recovery in placebo versus metformin (i) Heat map of senescence/SASP and inflammatory related transcripts after recovery as a fold change from PRE. (j–p) Transcriptional changes of cellular senescence driving transcripts as a fold change from PRE, at DAY1, POST, and REC. Log10 Adjusted 