Glutamine-stimulated in vitro hypertrophy is preserved in muscle cells from older women
Introduction
Sarcopenia in older population is a condition characterized by an accentuated decline in skeletal muscle mass leading to adverse outcomes such as physical disability, loss of autonomy and poor quality of life (Cruz-Jentoft et al., 2019; Goodpaster et al., 2006). The maintenance of muscle mass depends on the dynamic balance between muscle protein synthesis (MPS) and protein breakdown. Although a gradual decline in basal post-absorpive MPS has been associated with the age-related loss of muscle mass (Short et al., 2004), other studies did not find any detectable changes in basal MPS rates with healthy aging (Phillips et al., 2017; Volpi et al., 2001). Currently, it is suggested that the loss of muscle mass in healthy older adults is mainly the consequence of an anabolic resistance, defined as a reduced MPS stimulation in response of an anabolic stimulus (e.g. nutrient intake, hormonal stimulation or muscle contraction) (Morton et al., 2018). Indeed, greater post-prandial MPS stimulation in response to amino acid (AA) ingestion is found in young compared to older adults (Katsanos et al., 2006; Wall et al., 2015). However, other studies reported similar MPS responses in young and older adults in response to optimized AA-based supplementation (Koopman et al., 2009; Moore et al., 2015).
The exact etiology of anabolic resistance to AA remains unclear, and some putative extrinsic factors have been proposed: impaired AA digestion and absorption, reduced blood flow and skeletal muscle microvascular perfusion, and low tissue AA uptake (Mitchell et al., 2017). Alternatively, intrinsic defects at the level of the muscle cell may compromise the AA-induced activation of the mechanistic target of rapamycin (mTOR) pathway, the major anabolic pathway controlling MPS (Schiaffino et al., 2013). In this respect, the in vitro exploration of human primary myogenic cells provides a relevant approach to study the intrinsic behavior of muscle cells from older population, while excluding potential influences of circulating and environmental factors. To date, there are no reports exploring the anabolic resistance to AA supplementation in human myogenic cells from older adults. Therefore, the present study aims to investigate the anabolic response to glutamine supplementation (cell size, differentiation capacity, protein synthesis and mTOR pathway) in human myogenic cells from a sample of young and older women. Glutamine was selected based on our recent study showing that it acts as a strong anabolic stimulus inducing both myotube hypertrophy and activation of protein synthesis (Rantala and Chaillou, 2019). The relevance of this AA is further underlined by the fact that glutamine is the major source of amino acids within the entire intramuscular pool of amino acids (more than 60 %) (Bergstrom et al., 1974), representing the main bulk of intramuscular free amino acids.
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Subjects and anthropometrics
Eight young (YW, age 21–35 years) and eight older (OW, age 65–70 years) healthy and recreationally active women were recruited for this study. The subjects included in this study participated in various recreational physical activities including walking, swimming, jogging, cycling, Nordic walking and skiing. Three young women participated in recreational resistance training, while none of the older women engaged in strengthening activitites. Participants included in this study had a body mass
Body composition and functional capacity
Results of body composition, muscle strength and cardiorespiratory fitness in YW and OW are presented in Table 1. Higher percentage of body fat, lower skeletal muscle mass (SMM) and skeletal muscle index (SMI) were observed in OW compared to YW. OW had also lower maximal dynamic strength in leg extension (1-RM LE) and aerobic fitness (VO2max) compared to YW. The age-related difference in muscle strength (1-RM LE) was greater than that observed for muscle mass (- 33 % and - 20 %, respectively),
Discussion
This study is to our knowledge the first to explore the intrinsic capacity of muscle cells from young and older adults to respond to a nutritional stimulus. We demonstrated that GLUT-induced myotube hypertrophy and protein synthesis are preserved in healthy older women.
Previous in vitro studies investigating the differentiation capacity of myogenic cells during aging included a limited number of subjects, provided little information about physiological characteristics or were characterized by a
Funding
This work was supported by the Swedish Research Council for Sport Science and by the foundation Lars Hiertas Minne (FO2018-0231 to T.C).
Author contributions
FK and TC designed the study. TC and IS carried out experimental studies and data analyses. TC, IS and FK wrote the manuscript. TC, IS and FK approved the final version of the manuscript.
Declaration of Competing Interest
None.
Acknowledgments
We thank Dr Stefan Särnblad (Department of Pediatrics, University Hospital Örebro) for his helpful contribution to the collection of muscle biopsies.
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Thomas Chaillou and Igor Sanna equally contributed to this work.