A Comparison Of Differing Modalities Of Exercise on the Acute Satellite Cell Responses in Older Adults

Abstract

Introduction: A hallmark of the human aging process is the gradual loss of muscle mass and strength, a phenomenon commonly referred to as sarcopenia. Although sarcopenia is likely the result of both a reduction in fiber size and a loss of muscle fibers, it has become abundantly clear that sarcopenia is primarily characterized by the reduction in type II fiber size. The mechanism(s) driving this fiber type-specific loss still remain largely unknown, but it has become evident that the dysregulation of a muscle-specific stem cell population called satellite cells (SC) plays an important role in its progression. Luckily, older adults still retain the ability to activate and expand their SC in response to exercise; what remains unclear is which modality of exercise is optimal for promoting SC contribution to skeletal muscle remodelling. We sought to test the hypothesis that both resistance exercise (RE) and high-intensity interval training (HIIT) would stimulate greater expansion of SC when compared to traditional aerobic exercise (AE). Furthermore, we also sought to determine potential extrinsic/intrinsic factors that might contribute to regulating the differences in SC behavior across the different modalities of exercise

Methods: Sedentary older men (n=22; 67 ± 4 yr; BMI: 27.0 ± 2.6 kg•m-2 [mean ± SEM]) were randomly assigned to complete an acute bout of either RE (3 sets of leg extensor and press, 95% 10RM, n = 7), HIIT (10 x 1min, 95% maximal heart rate [HRmax], n= 8) or AE (30min, 55-60% HRmax. n = 7). Muscle biopsies were obtained before and at 24h and 48h following each exercise bout, while blood samples were taken before and at 24h after exercise. The SC response was analyzed using immunofluorescent microscopy and whole-muscle mRNA analysis, while the variability in exercise-induced muscle damage (EIMD) was estimated by analyzing serum samples for creatine kinase (CK) concentration.

Results: The muscle SC content increased 45% (p < 0.001) and 52% (p = 0.001) relative to baseline at 24h and 48h respectively following RE, while HIIT stimulated a significant increase of 33% (p = 0.007) at 48h. Fiber type-specific analysis further revealed that both RE and HIIT were capable of inducing significant increases in both type I and type II-specific SC by 48h post-exercise. Further analysis of individual SC responses also revealed a correlation (r = 0.737, p < 0.001) between the change in SC content across the acute time-course and the relative change in creatine kinase (CK) activity levels 24h post-exercise. The lack of any notable SC expansion following AE was to some degree explained by insufficient changes to cell cycle and myostatin (MSTN)-related genes. Conversely, RE produced the greatest reduction in MSTN mRNA over the 48h time-course while inducing a noticeable decrease of 124% in SMAD3 (a mediator of MSTN signaling) mRNA at 48 post-exercise.

Conclusions: These data illustrate that RE is the most potent stimulator of acute SC activity in older men, while also showing for the first time that of HIIT can induce a SC response in the same population. The positive relationship between the changes in SC content in response to exercise and CK activity levels suggests that the level of muscle damage induced by an exercise type may influence the magnitude of the subsequent SC response. The magnitude of each SC response is also likely influenced by unique changes in MSTN signaling that follow each modality of exercise.