Identification of Key Factors Which Induce Different Exercise Effects

Skeletal muscle is the primary organ responding to exercise. As known, exercise initiates muscle regeneration to strengthen muscle, but its phenotypes vary upon types of exercise. Endurance exercise mainly drives formation of type 1 slow-twitch muscle fiber while resistant exercise does formation of type 2 fast-twitch muscle fiber. However, it is not clear by which mechanism these highly characterized forms of muscle regeneration arise upon each exercise type. Here, we hypothesize that differences in effects of different types of exercise fundamentally originate from such distinct modalities of muscle regeneration. As such, we aim to determine detailed molecular mechanisms of muscle regeneration upon different types of exercise in order to ultimately unravel how different types of exercise have differential effects on our body.

To this end, experimentally, we plan to generate three groups of mice: sedentary condition, endurance exercise, resistance exercise. By comparing results of bulk RNA-seq and proteomics in those groups, we will identify genomic and proteomic differences of muscle cells, respectively, in unbiased manner. In addition, since muscle regeneration occur through differentiation of muscle stem cells called satellite cells into myoblasts which further differentiate into myotubes, we will study the features of satellite cells upon each type of exercise using single-cell RNA-seq analysis. With this plan, we will identify crucial factors in determining specific muscle types upon exercise, and categorize satellite cells upon each exercise. These outcomes will lead to future experiments revealing detailed mechanism of exercise-type specific muscle regeneration considering those factors or satellite cells as critical players in muscle regeneration upon exercise.

Based on understanding of molecular mechanism of muscle regeneration upon endurance exercise and resistance exercise, we will further expand our understanding to investigate mechanism that enable exercise group to regenerate muscle more efficiently than sedentary group upon pathological injury. We will parameterize factors found to be important in muscle regeneration upon exercise and compare those parameters in exercise group with respect to sedentary group after giving pathological injury. Finally, we plan to utilize factors discovered to improve muscle regeneration upon pathological muscle injury to treat disease models including Duchenne muscular dystrophy (DMD), amyotrophic lateral sclerosis (ALS) or any related muscle diseases, etc.

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2)Lee, S., et al., PLOS, 2007