Presentation description

Skeletal muscle gives us the strength and mobility we rely on for daily life. However, with aging, disuse, or illness, muscles can atrophy, leading to reduced strength, mobility, and overall health, especially in older adults. While the hormonal and inflammatory causes of muscle loss are well known, how epigenetic mechanisms contribute to muscle decline, and how they might protect muscle and support recovery, is not fully understood.

One type of epigenetic modification is histone methylation, which affects how tightly DNA is packaged and thus how genes are expressed. SMYD1 (SET and MYND domain-containing protein 1) is a muscle-specific histone methyltransferase that adds methyl groups to histones, regulating gene expression in cardiac and skeletal muscle. Although well studied in heart development, its role in adult skeletal muscle maintenance remains unclear. In vitro studies show SMYD1 is essential for myotube differentiation in mouse muscle (C2C12) cells (1); its downregulation impairs myoblast differentiation under carcinogenic stress (2), suggesting that maintaining or increasing SMYD1 may help protect muscle under catabolic stress. This project tests the novel hypothesis that increased SMYD1 expression can reduce muscle atrophy and improve recovery.

To investigate this, we use serum starvation of differentiated C2C12 myotubes as an in vitro model of catabolic stress. Our design includes three groups: (1) SMYD1 overexpression (via adenovirus), (2) atrophic conditions induced by serum starvation, and (3) atrophic conditions combined with SMYD1 overexpression. SMYD1 expression levels are quantified by qPCR and confirmed by Western blotting using biological replicates; statistical analysis uses a t-test.

Although data collection is ongoing, this is the first analysis of SMYD1 in skeletal muscle under these conditions. Findings will advance our understanding of SMYD1's protective role in muscle atrophy, provide essential data for future in vivo studies, and guide research toward SMYD1-targeted therapies to help prevent muscle loss in vulnerable populations.