Skeletal Muscle Transcriptome Alterations Related to Declining Physical Function in Older Mice

Area of Science:

• Gerontology and Muscle Physiology
• Molecular Biology and Genomics

Background:

• Aging leads to decreased physical function and exercise capacity, partly due to muscle tissue changes.
• Age-related changes in skeletal muscle gene expression are hypothesized to correlate with functional decline.

Purpose of the Study:

• To investigate the relationship between age-related differentially expressed genes (DEGs) in skeletal muscle and age-associated declines in physical function.
• To identify specific gene expression patterns associated with functional status in aging mice.

Main Methods:

• Skeletal muscle (tibialis anterior) samples were collected from male C57BL/6 mice at 6, 24, and 28 months of age.
• Next-Generation Sequencing (RNAseq) was used to identify DEGs between age groups (6m vs. 24m and 6m vs. 28m).
• Physical function was assessed using a comprehensive functional assessment battery (CFAB), and gene expression was correlated with CFAB scores.

Main Results:

• A five-fold increase in DEGs was observed in 28-month-old mice compared to 24-month-old mice.
• Numerous DEGs showed a strong association (R ≥ |0.70|) with physical function status in older mice.
• Gene ontology analysis highlighted enriched pathways in axon guidance and acetylcholine receptors, suggesting a role for denervation/reinnervation.

Conclusions:

• Specific age-related DEG patterns are linked to diminished physical function.
• The findings suggest a potential acceleration of the aging process in mice between 24 and 28 months of age.
• Denervation/reinnervation dynamics may be critical in age-related functional decline.