GENES RELATED TO MITOCHONDRIAL HEALTH IN MYOBLASTS ARE NEGATIVELY IMPACTED WITH AGE BUT MAY BE RESCUED WITH EXERCISE-ASSOCIATED PATHWAY STIMULATION DURING EARLY MYOGENESIS
Emily L. Zumbro1, Anthony A. Duplanty2, Ryan A. Gordon3, Gena D. Guerin4, Matthew L. Sokoloski2, Monique J. LeMieux2, Vic Ben-Ezra2, Kyle Biggerstaff2. 1University of Alabama at Birmingham, Birmingham, AL. 2Texas Woman's University, Denton, TX. 3Drury University, Springfield, MO. 4Penn State Harrisburg, Harrisburg, PA.
BACKGROUND: Skeletal muscle (SKM) health is impacted by the aging process and results in delayed regeneration and mitochondrial dysfunction. The purpose of this study is to investigate the molecular effects of an in vitro SKM myoblast aging protocol in combination with a β-2 adrenergic receptor agonist treatment on the expression of genes related to mitochondrial health. METHODS: Human SKM myoblasts (n = 6 per group) were cultured (3 x 105 seeding density) and proliferated to 85% confluency upon extraction. Groups included control cells (CON), aged cells (AGED), CON plus formoterol stimulation (CON + FORM; 30nM for 3h), and AGED plus FORM stimulation (AGED + FORM; 30nM for 3h). AGED myoblasts were passaged 18 times to exhibit reduced proliferative properties experienced in SKM of older adults, whereas CON myoblasts were analyzed at passage 5. qPCR analyses included the following genes: Nuclear Respiratory Factor (NRF1), Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha/Beta (PGC-1α/β), Superoxide Dismutase 2 (SOD2), Mitochondrial Transcription Factor A (TFAM), and Glutathione Synthetase (GSS). Data were analyzed via one-way ANOVA followed by Games-Howell post-hoc analyses with a Welch correction. Data are expressed as mean ± SEM. RESULTS: PGC1-β: CON + FORM (3.03 ± 0.43) was greater than CON (1.00 ± 0.14, p = 0.02); AGED + FORM (4.35 ± 0.51) was greater than CON (1.00 ± 0.14, p < 0.01) and AGED (1.49 ± 0.20, p = 0.01). TFAM: CON + FORM (2.92 ± 0.38) was greater than CON (1.00 ± 0.16, p = 0.01). NRF1, PGC1-α, SOD2, and GSS: No significance between groups. All reported differences are significant. CONCLUSIONS: Although our results within the AGED and AGED + FORM groups were not significant, likely due to high inter group variance, we found evidence of genetic dysregulation. Increases in SOD2 and GSS expression in the AGED group indicate increased oxidative stress, which potentially decreased in response to FORM stimulation. The potential presence of increased oxidative stress may influence the increase in mitochondrial biogenesis-related gene expression to combat this oxidative stress and reduce mitochondrial dysfunction. FORM appears to stabilize mitochondrial biogenesis-related genes in AGED myoblasts, indicating improved overall mitochondrial health.
Zumbro, EL; Duplanty, AA; Gordon, RA; Guerin, GD; Sokoloski, ML; LeMieux, MJ; Ben-Ezra, V; and Biggerstaff, K
"GENES RELATED TO MITOCHONDRIAL HEALTH IN MYOBLASTS ARE NEGATIVELY IMPACTED WITH AGE BUT MAY BE RESCUED WITH EXERCISE-ASSOCIATED PATHWAY STIMULATION DURING EARLY MYOGENESIS,"
International Journal of Exercise Science: Conference Proceedings: Vol. 16:
1, Article 63.
Available at: https://digitalcommons.wku.edu/ijesab/vol16/iss1/63