Age-dependent skeletal muscle transcriptome response to bed rest-induced atrophy

Area of Science:

• Skeletal Muscle Physiology
• Molecular Biology
• Aging Research

Background:

• Short-term muscle disuse leads to significant muscle loss, particularly in older adults.
• Aging may accelerate muscle loss during periods of inactivity.
• Understanding transcriptional changes during disuse can identify therapeutic targets.

Purpose of the Study:

• To compare the muscle transcriptome between young and older adults following a period of bed rest.
• To identify candidate genes and pathways associated with muscle loss induced by disuse in aging.
• To investigate potential therapeutic targets for combating muscle atrophy.

Main Methods:

• RNA sequencing of muscle biopsies from young and older adults before and after 5-day bed rest.
• Bioinformatic analysis using DESeq (R) to identify differentially regulated genes and pathways.
• Comparison of transcriptional profiles between age groups and correlation with changes in leg lean mass.

Main Results:

• Older adults exhibited greater alterations in mechanosensing and cell adhesion pathways (e.g., Actin Cytoskeleton, ILK, RhoA, Integrin Signaling) compared to young adults.
• Hepatic Fibrosis/Hepatic Stellate Cell Activation pathway was significantly altered only in older adults.
• Unique upregulation of inflammation and muscle wasting genes (CXCL2, GADD45A) and downregulation of MAFB in older adults post-bed rest, with MAFB correlating to leg lean mass loss.

Conclusions:

• Skeletal muscle dysregulation during short-term disuse in older adults is linked to altered fibrosis, inflammation, and cell adhesion pathways.
• Specific gene expression patterns in older adults may indicate a predisposition to muscle loss.
• Findings suggest mechanistic-based therapies targeting these pathways could combat age-related muscle atrophy.