Skeletal Muscle Gene Expression Study of Monozygous Twins with 35 Years of Divergent Exercise History

Abstract

Variations in physical ability and capacities among individuals depend on both genetic inheritance and lifestyle. Previous research has yet to utilize a human model of monozygous (MZ) twins with substantial and long-term differences in exercise backgrounds to identify molecular and cellular mechanisms underlying exercise-mediated adaptations in muscle and whole-body phenotype. PURPOSE: In particular, this study examined skeletal muscle expression of genes related to muscle growth, inflammation, metabolism, and fiber type distribution in MZ twins with 35 years of substantially differing exercise history. METHODS: Muscle biopsies were collected from the vastus lateralis of male, 52-year-old MZ twins. Reverse transcriptase-polymerase chain reaction was used for the quantification of mRNAs associated with the following gene markers of various adaptive responses: a) skeletal muscle fiber type shift: MyHC-1, MyHC-2a, and MyHC-2x; b) adaptations in oxidative capacity: transcription factor A of the mitochondria (TFAM), and citrate synthase; c) angiogenesis: endothelial nitric oxide synthase, and vascular endothelial growth factor; d) muscular growth and satellite cell activation: myostatin, Pax7 (PAX7), mechano-growth factor (IGF1Ec), insulin-like growth factor a (IGF1Ea), and MyoD; and e) the inflammatory response: TWEAK (TNFSF12), the FN14 TWEAK receptor (TNFRSF12A) and tumor necrosis factor-α (TNF). RESULTS: MyHC-2x was expressed at a lower level in the trained subject relative to the untrained subject. No differences were observed for other markers of fiber type or metabolic or angiogenesis gene products. Some differences were observed in the expression of genes related to muscle growth including elevations in PAX7, MGF and IGF1Ea, and a reduction in MyoD. Finally, the only difference in expression of markers for the inflammatory response was an elevation in TNFRSF12A in the trained twin. CONCLUSIONS: At the mRNA-level, differences in expression of some key markers related to muscle fiber type, muscle growth, and the inflammatory response were observed in the trained vs the untrained twin. These data highlight the adaptability of skeletal muscle at the molecular level with decades of divergent physical activity patterns.