Related Experiment Video
Updated: Feb 20, 2026
In Situ Immunofluorescent Staining of Autophagy in Muscle Stem Cells
Published on: June 12, 2017
The effect of ARC ablation on skeletal muscle morphology, function, and apoptotic signaling during aging
Kira Vorobej1, Andrew S Mitchell1, Ian C Smith1
1Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
Abstract:
Augmented apoptotic signaling can result in degradation of skeletal muscle proteins and loss of myonuclei, ultimately contributing to muscle atrophy and contractile dysfunction. Apoptosis repressor with caspase recruitment domain (ARC) is an anti-apoptotic protein highly expressed in skeletal muscle. Here we examined the role of ARC on age-related skeletal muscle apoptosis and wasting by utilizing an ARC-deficient mouse model. Aged mice displayed a number of morphological, phenotypic, and contractile alterations in both soleus and plantaris muscle with aging. Although no differences were found in proteolytic enzyme activity, ARC protein decreased while several anti-apoptotic proteins (e.g., BCL2, BCLXL, HSP70, and XIAP) and the release of mitochondrial housed protein (i.e., SMAC, AIF) increased in aged muscle. Importantly, ARC KO mice had low muscle weights and fewer fibers in soleus, with 2-year-old ARC KO mice displaying lower mitochondrial BCL2 protein along with augmented release of CYTC and SMAC in red/oxidative muscle. Overall, these results indicate that aged skeletal muscle undergoes atrophy as well as contractile and fiber type composition alterations despite an increase in anti-apoptotic protein expression. Although some mitochondrial-specific apoptotic alterations occurred in skeletal muscle due to ARC ablation over the lifespan, our data suggest that ARC may not have a large influence during skeletal muscle aging.
Insights
Apoptosis repressor with caspase recruitment domain (ARC) levels decrease in aged skeletal muscle, but ARC deficiency did not significantly worsen age-related muscle loss or apoptosis, suggesting ARC has a limited role in muscle aging.
Area of Science:
- Cellular and Molecular Biology
- Skeletal Muscle Physiology
- Aging Research
Background:
- Apoptosis contributes to skeletal muscle atrophy and dysfunction.
- Apoptosis repressor with caspase recruitment domain (ARC) is a key anti-apoptotic protein in skeletal muscle.
- Age-related muscle wasting involves complex cellular signaling pathways.
Purpose of the Study:
- To investigate the role of ARC in age-related skeletal muscle apoptosis and wasting.
- To analyze the impact of ARC deficiency on muscle morphology, phenotype, and function during aging.
- To determine if ARC ablation exacerbates age-associated muscle decline.
Main Methods:
- Utilized an ARC-deficient (ARC KO) mouse model.
- Compared aged wild-type mice with aged ARC KO mice.
- Assessed muscle morphology, protein expression (apoptotic and anti-apoptotic markers), proteolytic activity, and mitochondrial protein release.
Main Results:
- Aged mice showed muscle alterations, decreased ARC protein, and increased anti-apoptotic proteins and mitochondrial protein release.
- ARC KO mice exhibited reduced muscle weight and fiber count.
- Specific mitochondrial apoptotic alterations were observed in ARC KO mice, but ARC deficiency did not significantly worsen overall age-related muscle atrophy.
Conclusions:
- Skeletal muscle aging involves atrophy and functional changes despite increased anti-apoptotic protein expression.
- ARC ablation leads to some mitochondrial apoptotic changes but appears to have a limited role in the overall process of age-related skeletal muscle aging.
Related Concept Videos
01:19The Effect of Aging on Tissues
01:26Cross-bridge Cycle