Longitudinal transcriptomic analysis of mouse sciatic nerve reveals pathways associated with age-related muscle...

Area of Science:

• Neuroscience
• Gerontology
• Molecular Biology

Background:

• Sarcopenia, characterized by age-related loss of muscle mass and strength, is increasingly recognized to involve neural components.
• Accumulating evidence suggests that the origins of sarcopenia may lie in the neural pathways controlling skeletal muscles.

Purpose of the Study:

• To identify early molecular alterations in the sciatic nerve that may drive the initiation of sarcopenia.
• To investigate the longitudinal transcriptomic changes in the sciatic nerve of aging mice.

Main Methods:

• Longitudinal transcriptomic analysis (RNA sequencing) of the sciatic nerve from aging mice (5 to 24 months old).
• Validation of differentially expressed genes (DEGs) using quantitative reverse transcription PCR (qRT-PCR).
• Functional enrichment analysis of gene expression patterns and confirmation of muscle aging and denervation markers.

Main Results:

• 51 significant DEGs were detected in the sciatic nerve of 18-month-old mice compared to 5-month-old mice.
• Up-regulated genes were associated with the AMP-activated protein kinase signaling pathway and circadian rhythm.
• Down-regulated genes were linked to biosynthesis and metabolic pathways, with extracellular matrix organization and immune response implicated in sarcopenia initiation.

Conclusions:

• Gene expression changes in the peripheral nerve were observed before muscle denervation and sarcopenia onset.
• These early molecular changes provide novel insights into the biological processes underlying sarcopenia initiation and pathogenesis.
• Further research is needed to explore the potential of these findings as disease modifiers or biomarkers for sarcopenia.