Sex-specific alteration in human muscle transcriptome with age

Area of Science:

• Gerontology
• Molecular Biology
• Genetics

Background:

• Sarcopenia, an age-related decline in muscle mass and strength, disproportionately affects males and females.
• The precise molecular mechanisms underlying sarcopenia's sex-specific pathophysiology remain poorly understood.

Purpose of the Study:

• To identify age-associated differentially regulated genes in human gastrocnemius muscle.
• To investigate sex-specific molecular differences in aging skeletal muscle.

Main Methods:

• Analysis of human gastrocnemius muscle transcriptomes from aged males and females.
• Identification of differentially expressed genes using a twofold expression threshold.
• Gene Ontology (GO) enrichment analysis to determine pathway involvement.

Main Results:

• Identified 269 age-differentially regulated genes in total muscle samples.
• Found 239 differentially regulated genes in aged female muscle, including novel genes like KIF20A and TRPV6.
• Detected 166 differentially regulated genes in aged male muscle, including novel genes like CENPK and CDKN2A.
• Discovered distinct pathway disruptions: glucose catabolism in females, replicative senescence in males.

Conclusions:

• Age-related sarcopenia exhibits significant sex-specific molecular differences.
• Novel genes and pathways identified offer potential sex-specific therapeutic targets.
• Targeting these molecular differences may combat sarcopenia and promote healthy aging.