Transcriptomic Signatures of Skeletal Muscle Adaptation: Disuse, Rehabilitation, and Resistance Exercise Intervention

Skeletal muscle, a dynamic tissue essential for movement and metabolic regulation, undergoes significant changes with age, leading to sarcopenia characterized by muscle mass decline and functional impairment. Moreover, short-term inactivity exacerbates sarcopenia, necessitating effective rehabilitation strategies. Despite advancements in understanding muscle physiology, the transcriptional events underlying muscle atrophy and hypertrophy remain elusive. In this dissertation, we first aimed to elucidate the effects of disuse on the skeletal muscle transcriptome and map the molecular time course of rehabilitation. By employing transcriptomic analyses, we identified key molecular pathways altered following disuse, including mitochondrial function, apoptosis, immune signaling, and inflammation. We further observed that disuse negatively affects pathways associated with adaptation to resistance exercise. Lastly, we observed that pathways involved in inflammation, mitochondrial function, and protein synthesis are time-dependent, and are enriched at different timepoints during rehabilitation. The second aim of this dissertation was to determine the age-dependent and -independent effects of resistance exercise training on the transcriptome. Primary findings included that resistance exercise training significantly downregulated pathways associated with muscle aging, including cellular senescence, and activating transcription factor 4 (ATF4). Additionally, we used a novel approach to gene set enrichment analysis (GSEA) to determine which biological pathways are associated with improvements in important muscle phenotypes including lean mass and strength. We revealed that pathways associated with mitochondrial function are positively correlated with lean mass, whereas pathways associated with translation, rRNA processing, and polyamine metabolism are positively correlated with strength. In summary, our study unveils novel insights into the molecular mechanisms driving skeletal muscle responses to disuse and resistance exercise training. By integrating transcriptomic analyses with functional assessments, we identify key pathways implicated in muscle adaptation and aging. These findings offer potential therapeutic targets for combating sarcopenia and highlight the importance of personalized exercise interventions tailored to individual needs and physiological states.

Name thesis:degree_name

Doctor of Philosophy

Grantor

The University of Texas Medical Branch at Galveston

Year dc:date.issued

2024

Author dc:creator

• Von Ruff, Zachary

Advisors dc:contributor.advisor

• Murton, Andrew
• Lantz, Emily
• Villasante-Tezanos, Alejandro
• Adams, Christopher
• Rasmussen, Blake (rasmussenb@uthscsa.edu)

Language dc:language.iso

English

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/12690

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/12690