Satellite cells are required for muscle regeneration, remodeling, and repair through their activation, proliferation, and differentiation; however, how dietary factors regulate this process remains poorly understood. The L-Type amino acid transporter 1 (LAT1) transports amino acids, such as leucine, into mature myofibers, which then stimulates protein synthesis and anabolic signaling. However, whether LAT1 is expressed on myoblasts and is involved in regulating myogenesis is unknown. The aim of this study was to characterize the expression and functional relevance of LAT1 during different stages of myogenesis and in response to growth and atrophic conditions in vitro. We determined that LAT1 is expressed by C2C12 and human primary myoblasts, and its gene expression is lower during differentiation (p<0.05). Pharmacological inhibition and genetic knockdown of LAT1 impaired myoblast viability, differentiation, and fusion (all p<0.05). LAT1 protein content in C2C12 myoblasts was not significantly altered in response to different leucine concentrations in cell culture media or in two in vitro atrophy models. However, LAT1 content was decreased in myotubes under atrophic conditions in vitro (p<0.05). These findings indicate that LAT1 is stable throughout myogenesis and in response to several in vitro conditions that induce muscle remodeling. Further, amino acid transport through LAT1 is required for normal myogenesis in vitro.

Resistance training combined with adequate protein intake supports skeletal muscle strength and hypertrophy. These adaptations are supported by the action of muscle stem cells (MuSCs) which are regulated, in part, by fibro-adipogenic progenitors (FAPs) and circulating factors delivered through capillaries. It is unclear if middle-aged males and females have similar adaptations to resistance training at the cellular level. To address this gap, 27 (13 males, 14 females) middle-aged (40-64 years) adults participated in 10-weeks of whole-body resistance training with dietary counselling. Muscle biopsies were collected from the vastus lateralis pre- and post-training. Type II fibre cross-sectional area increased similarly with training in both sexes (P = 0.014). MuSC content was not altered with training; however, training increased PDGFRα+/CD90+ FAP content (P < 0.0001) and reduced PDGFRα+/CD90- FAP content (P = 0.044), independent of sex. The number of CD31+ capillaries per fibre also increased similarly in both sexes (p<0.05). These results suggest that muscle fibre hypertrophy, stem/progenitor cell, and capillary adaptations are similar between middle-aged males and females in response to whole-body resistance training.

Human skeletal muscle is a remarkedly plastic tissue that has a high capacity to adapt in response to various stimuli. These adaptations are due in part to the function of muscle-resident stem/progenitor cells. Skeletal muscle regeneration and adaptation is facilitated by the activation and expansion of muscle stem cells (MuSCs). MuSC fate is regulated by signals released from cells in their niche, such as fibro-adipogenic progenitors (FAPs), as well as a variety of non-cellular niche components. Sufficient dietary protein consumption is critical for maximizing skeletal muscle adaptation to exercise and maintaining skeletal muscle in disease; however, the role of dietary protein in altering MuSC and FAP responses to exercise in healthy populations and skeletal muscle disease states requires more research. The present review provides an overview of this emerging field and suggestions for future directions. The current literature suggests that in response to resistance exercise, protein supplementation has been shown to increase MuSC content and the MuSC response to acute exercise. Similarly, protein supplementation augments the increase in MuSC content following resistance training. Endurance exercise, conversely, is an area of research that is sparse with respect to the interaction of protein supplementation and exercise on muscle stem/progenitor cell fate. Initial evidence suggests that protein supplementation augments the early myogenic response to acute endurance exercise but does not enhance the MuSC response to endurance training. Resistance training increases the number of proliferating FAPs with no additional effect of protein supplementation. Future research should continue to focus on the nutritional regulation of skeletal muscle stem/progenitor cell fate paired with studies examining the effects of exercise on a variety of human populations.

We recently demonstrated that sweating‐induced hypohydration attenuated whole‐body heat loss (via reduced sweat evaporation) in young but not middle‐aged men during exercise‐heat stress. In that work, we reasoned that this divergent response may stem from an attenuated influence of intravascular osmolality (elevated during hypohydration) on heat dissipation in the middle‐aged. This hypothesis is supported by previous studies showing i) increased osmolality attenuates sweating in young adults and ii) fluid‐regulatory responses to osmotic stimuli are blunted with aging. However, the independent effect of intravascular osmolality on whole‐body heat loss and thermal strain in middle‐aged men during exercise has not been directly evaluated. On two separate occasions, six young (25 years [SD 4]) and eight middle‐aged‐to‐older (61 years) men underwent a 90‐min intravenous infusion of either 0.9% saline (200 [5] μmL·min−1·kg−1; ISO) or 3.0% saline (125 μmL·min−1·kg−1; HYP). Participants then performed 60 min of cycling at a fixed metabolic heat production of 250 W·m−2 in dry heat (40ºC, ~15% relative humidity). Serum osmolality and plasma volume responses were determined from venous blood samples procured at baseline (prior to infusion) and end‐exercise (60‐min). Heat production and whole‐body heat loss (evaporative + dry heat loss) were measured via indirect and direct calorimetry, respectively. Rectal temperature was monitored continuously. End‐exercise serum osmolality was elevated in HYP compared to ISO in the young (309 [4] vs 299 [3] mOsm·kg−1; p<.001) and middle‐aged‐to‐older (312 [2] vs 300 [4] mOsm·kg−1; p<.001) men and was similar between age‐groups (both p≥.07). In the young, the reduction in plasma volume from baseline at end‐exercise was greater in ISO relative to HYP (−8 [3] vs −4 [3]%; p=.014). By contrast, no differences in the plasma volume response were detected between ISO and HYP in the older group (−9 [4] vs −4 [6]%; p=.14). Changes in plasma volume were similar between age‐groups in each condition (both p≥.75). Whole‐body heat loss was attenuated in HYP compared to ISO in the young (233 [13] vs 251 [15] W·m−2; p=.012), whereas no effect of osmolality was observed in the middle‐aged‐to‐older men (225 [14] vs 227 [16] W·m−2; p=.74). Further, heat loss was attenuated in the middle‐aged‐to‐older vs young in ISO (p=.017) but was comparable between groups in HYP (p=.26). Similarly, a greater end‐exercise rectal temperature was noted in HYP vs ISO in the young (38.2 [0.3]°C vs 37.9 [0.3] °C; p=.037) but not the middle‐aged‐to‐older men (38.3 [0.3]°C vs 38.3 [0.3]°C; p=.88). The rectal temperature response was greater in the middle‐aged‐to‐older during ISO (p=.013) whereas no difference between age‐groups was observed in HYP (p=.59). Our findings indicate that whole‐body heat loss and rectal temperature responses to exercise in dry‐heat are not appreciably modified by increased serum osmolality in middle‐aged‐to‐older men. An age‐related reduction in osmotic sensitivity may therefore explain the blunted eff...

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