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<p>We previously reported that resistance trained (T) and untrained (UT) individuals exhibit similar targeted molecular responses in skeletal muscle following two weeks of leg immobilization and eight weeks of subsequent recovery resistance training (RT). The present analysis examined the skeletal muscle transcriptome, microRNA (miR)-ome, and proteome responses in a subset of these participants (<i>N</i> = 8 T and <i>N</i> = 8 UT). Vastus lateralis biopsies were obtained at baseline (PRE), after the 2-wk immobilization protocol (DIS), and after 8-wk of recovery RT (REC-RT). Tissue RNA and protein were subjected to RNA- and miR-sequencing and proteomics, respectively. Analyses included: (i) group and time differential expression (DE) and pathway enrichment for each independent -ome; (ii) multi-omics integration to reveal modules across the -omes; and (iii) leave one out cross-validated linear regression modeling (LOOCV) to reveal key features predictive of atrophy and hypertrophy. Most differentially expressed (DE) RNAs or differentially abundant (DA) proteins were time-driven rather than training status-driven. In all participants, the transcriptome was most responsive to disuse (PRE-to-DIS: 2047 DE mRNAs; 3 DE miRs; 10 DA proteins) while the transcriptome and proteome were both responsive to recovery RT (DIS-to-REC-RT: 446 DE mRNAs; 0 DE miR; 415 DA proteins). Pathways analyses revealed proteostasis and DNA repair with disuse atrophy, whereas striated muscle contraction, transcriptional regulation, and rRNA expression were enriched with recovery RT. Integrative analyses identified SLIT–ROBO signaling as a potentially novel axis in disuse atrophy, driven predominantly by transcriptomic changes, whereas enrichment of striated muscle contraction pathways in recovery RT was supported by coordinated mRNA and protein regulation. Via LOOCV, the 10 top predictors of disuse atrophy were RNAs (8 protein coding) primarily related to mitochondrial function and protein trafficking, while 9 of the top 10 predictors of recovery RT hypertrophy were RNAs (8 protein coding) related to membrane dynamics, ECM/cytoskeletal organization, and translation initiation. This integrative multi-omic approach reiterates that disuse atrophy and recovery RT-induced hypertrophy elicit similar molecular responses in T and UT individuals, highlighting distinct molecular signatures governing skeletal muscle atrophy and recovery hypertrophy independent of training status.</p>

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An integrative multi-omic analysis of skeletal muscle in response to disuse and recovery resistance training in resistance trained and untrained young adults

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • J. Max Michel,
  • Joshua S. Godwin,
  • Zachary A. Graham,
  • Jacob A. Siedlik,
  • Melissa D. Boersma,
  • Martino V. Franchi,
  • Harsimran S. Baweja,
  • C. Brooks Mobley,
  • Andreas N. Kavazis,
  • David C. Hughes,
  • Marcas M. Bamman,
  • Michael D. Roberts,
  • Christopher G. Vann

摘要

We previously reported that resistance trained (T) and untrained (UT) individuals exhibit similar targeted molecular responses in skeletal muscle following two weeks of leg immobilization and eight weeks of subsequent recovery resistance training (RT). The present analysis examined the skeletal muscle transcriptome, microRNA (miR)-ome, and proteome responses in a subset of these participants (N = 8 T and N = 8 UT). Vastus lateralis biopsies were obtained at baseline (PRE), after the 2-wk immobilization protocol (DIS), and after 8-wk of recovery RT (REC-RT). Tissue RNA and protein were subjected to RNA- and miR-sequencing and proteomics, respectively. Analyses included: (i) group and time differential expression (DE) and pathway enrichment for each independent -ome; (ii) multi-omics integration to reveal modules across the -omes; and (iii) leave one out cross-validated linear regression modeling (LOOCV) to reveal key features predictive of atrophy and hypertrophy. Most differentially expressed (DE) RNAs or differentially abundant (DA) proteins were time-driven rather than training status-driven. In all participants, the transcriptome was most responsive to disuse (PRE-to-DIS: 2047 DE mRNAs; 3 DE miRs; 10 DA proteins) while the transcriptome and proteome were both responsive to recovery RT (DIS-to-REC-RT: 446 DE mRNAs; 0 DE miR; 415 DA proteins). Pathways analyses revealed proteostasis and DNA repair with disuse atrophy, whereas striated muscle contraction, transcriptional regulation, and rRNA expression were enriched with recovery RT. Integrative analyses identified SLIT–ROBO signaling as a potentially novel axis in disuse atrophy, driven predominantly by transcriptomic changes, whereas enrichment of striated muscle contraction pathways in recovery RT was supported by coordinated mRNA and protein regulation. Via LOOCV, the 10 top predictors of disuse atrophy were RNAs (8 protein coding) primarily related to mitochondrial function and protein trafficking, while 9 of the top 10 predictors of recovery RT hypertrophy were RNAs (8 protein coding) related to membrane dynamics, ECM/cytoskeletal organization, and translation initiation. This integrative multi-omic approach reiterates that disuse atrophy and recovery RT-induced hypertrophy elicit similar molecular responses in T and UT individuals, highlighting distinct molecular signatures governing skeletal muscle atrophy and recovery hypertrophy independent of training status.