Skeletal Muscle Quality: A Biomarker for Assessing Physical Performance Capabilities in Young Populations

Muscle quality (MQ), defined as the amount of strength and/or power per unit of muscle mass, is a novel index of functional capacity that is increasingly relied upon as a critical biomarker of muscle health in low functioning aging and pathophysiological adult populations. Understanding the phenotypical attributes of MQ and how to use it as an assessment tool to explore the efficacy of resistance exercise training interventions that prioritize functional enhancement over increases in muscle size may have implications for populations beyond compromised adults, including healthy young adults who routinely perform physically demanding tasks for competitive or occupational purposes. However, MQ has received far less attention in healthy young populations than it has in compromised adults. Researchers and practitioners continue to rely upon static measures of lean mass or isolated measures of strength and power, rather than using MQ, to assess integrated functional responses to resistance exercise training and physical stress. Therefore, this review will critically examine MQ and the evidence base to establish this metric as a practical and important biomarker for functional capacity and performance in healthy, young populations. Interventions that enhance MQ, such as high-intensity stretch shortening contraction resistance exercise training, will be highlighted. Finally, we will explore the potential to leverage MQ as a practical assessment tool to evaluate function and enhance performance in young populations in non-traditional research settings.


INTRODUCTION
The ability of skeletal muscle to produce substantial force in relatively short periods of time is crucial to success in many sporting events, tactical operations, and activities of daily living. While the focus of improving muscular force generation traditionally centers on increasing muscle quantity (i.e., muscle hypertrophy), recent efforts have focused on improving muscle quality (MQ) for enhancing muscle function. MQ is an umbrella term referring to the ability of skeletal muscle to perform several functions effectively, including force production, contraction and relaxation, metabolism, substrate turnover and storage, heat generation, myokine production, and electrical conduction Correa-de-Araujo et al., 2017). Although no consensus definition of MQ exists as of yet, the ambiguity of the term has allowed investigators to examine several dimensions of MQ that relate to muscle function. As the most prominent function of skeletal muscle is force production, the present review will focus on MQ in this context; however, the role of skeletal muscle in other biological functions should not be overlooked.
In applied and clinical research settings, MQ is often quantified as muscle strength or power per unit of muscle mass (Barbat-Artigas et al., 2012;McGregor et al., 2014), commonly reported as peak force or maximal power production relative to a measure of muscle size, such as muscle volume or crosssectional area (CSA). This definition accounts for the functional significance of the architecture, the overall tissue characteristics of the skeletal muscle, and ultimately, force production capabilities (Mangine et al., 2020). Increased force output as a product of increased muscle mass is a well-established physiological concept (Bamman et al., 2000); however, research demonstrates that force generation is largely a product of skeletal MQ aside from muscle quantity (Ivey et al., 2000;Brooks et al., 2006;Goodpaster et al., 2006;Fukumoto et al., 2012). The distinction between MQ and muscle quantity is an important aspect of functional assessment, as two individuals with similar muscle mass may not be capable of producing equivalent amounts of force. Similarly and counterintuitively, individuals with smaller amounts of muscle mass may be more effective at producing force than those with greater amounts. Differences in MQ between individuals may help explain why certain muscles are stronger than others, despite similar sizes. However, MQ may also vary between limbs, generating potential for injury if not properly corrected.
Muscle quality has largely been studied in aging and adult populations with pathophysiological conditions, and in those studies, higher MQ is related to increased muscle strength, function, and physical performance, and vice versa Brown et al., 2016). As posited in this review, understanding the phenotypic attributes of MQ and using MQ as an assessment tool to explore the efficacy of exercise training that prioritizes functional enhancement over increases in muscle size may have implications for populations beyond compromised adults, including healthy young adults who routinely perform physically demanding tasks for competitive or occupational purposes. Accordingly, this review will critically examine MQ and the evidence base that supports MQ as a practical and important biomarker for functional capacity and performance in healthy, young populations. Interventions that augment MQ, such as high-intensity stretch shortening contraction resistance exercise training (RET), will be highlighted. Finally, we will explore the potential to leverage MQ as a practical assessment tool to evaluate function and performance enhancement in young populations in non-traditional research settings.

DISCERNING MQ FROM MUSCLE SIZE ALONE
One of the most important features of muscle is that it is dynamically regulated by changes in physical demands, as well as environmental challenges, and is remarkably plastic in response to various forms of stimuli (Caldow et al., 2015). One of the defining characteristics of exercise is its ability to initiate a complex assortment of highly coordinated molecular and cellular signaling events, as well as transcriptional regulators, which in turn have profound positive effects on muscle tissue (Bamman et al., 2014). Upon exposure to physical activity demands, muscle responds in a coordinated fashion by initiating various signaling events that drive changes in gene expression of intracellular processes, such as metabolism, alterations in hormone signaling, defense mechanisms against oxidative stress, DNA damage and repair, protein turnover, and muscle remodeling (Phillips et al., 2013;Camera et al., 2016). Thus, customary stimuli by appropriate activity or exercise prompt changes in gene expression, which ultimately results in an integrated physiological and functional adaptation in skeletal muscle and the surrounding soft tissue. Therefore, by solely examining changes in muscle size with exercise, the true exquisiteness of skeletal muscle functional adaptation is lost.
While the relationship between increased muscle size and increased force output is well-established, force generation is a result of several factors aside from exclusively mass (Ivey et al., 2000;Goodpaster et al., 2006;Fukumoto et al., 2012). The relationship between size and strength is not linear, as strength can be improved independently of significant increases in muscle growth (Parente et al., 2008;Dankel et al., 2017;Mattocks et al., 2017), and likewise, increases in size can occur without concomitant increases in force production (Ahtiainen et al., 2016;Jakobsgaard et al., 2018). Thus, beyond muscle size, other factors such as tissue composition (e.g., contractile and noncontractile components), architecture, metabolism, and neural activation contribute to the overall force production capabilities (McGregor et al., 2014). For example, lower-body CSA and volume are associated with greater adiposity (Varanoske et al., 2017), indicating that increased intramuscular fat may account for greater muscle volume. However, in this case, greater muscle size will likely not translate to greater force production. Factors contributing to muscle strength and size are listed in Table 1.
In this regard, muscle architectural characteristics that affect force production may change following RET, leading to improved muscle strength, power, and subsequently overall MQ. For instance, increases in fascicle length and pennation angle have been observed following RET (Kawakami et al., 1995;Aagaard et al., 2001;Blazevich et al., 2007;Seynnes et al., 2007;Baroni et al., 2013;Ema et al., 2013;Franchi et al., 2014Franchi et al., , 2016McMahon et al., 2014), with RET-induced increases in pennation angle implied to be associated with increased force production attributable to the degree of muscle hypertrophy experienced (Azizi and Brainerd, 2007;Ema et al., 2013). Interestingly, increases in fascicle length do not always accompany significant muscle hypertrophy (Fukutani and Kurihara, 2015), demonstrating that muscle force production is greater than just a factor of its size. Thus, measures of size alone, such as muscle CSA, inadequately estimate force production. This is why in recent years, sarcopenia has evolved from being defined exclusively as Relying exclusively on measures of strength (e.g., handgrip), size (e.g., CSA), or performance alone likely limits our ability to draw meaningful conclusions about the effectiveness of a training intervention because they do not tell a complete story. For instance, military body fat standards, which emphasize abdominal circumference measures and/or bioelectrical impedance analysis of body composition, not only have their own flaws when it comes to accuracy and reliability, but are also outdated because recruits today tend to have more body fat and more lean mass compared to previous generations, which aids in their ability to perform lifting and carrying tasks (Foulis et al., 2020). Moreover, there is an increased prevalence of those soldiers who are metabolically obese but normal weight, with low muscle mass and thus overall poor function (Foulis et al., 2020). Absolute handgrip strength is often used in clinical and research settings as a measure of muscle strength and function, but research has demonstrated that this is not the best indicator of function and that forearm MQ is a stronger predictor of physical performance (Abe et al., 2016). Because the majority of physically demanding tasks performed by younger individuals (e.g., load carriage during military operations) requires a combination of muscle strength, power, and size in order to maximize the potential of these individuals to perform their duties (Szivak, 2020), MQ should be viewed as a critically important metric for evaluating the capabilities of these individuals to maintain effective performance and reduce the likelihood of injury prior to deployment.

ASSESSMENT OF MQ
Measures of muscle size and function are often integrated into a single measure of MQ, termed relative strength (Correa-de-Araujo et al., 2017), which is more informative for laboratory or field studies when findings demonstrate improvements or declines in performance in response to a given stressor, or changes in muscle mass without associated changes in function. Relative strength can be calculated by measuring the strength or power of a muscle/muscle group divided by muscle mass. However, several methodologies of measuring muscle size and strength exist, resulting in limited consensus on the most appropriate way of assessing MQ. For instance, physical movement is often the result of several muscles working in synchrony to produce a desired effect, and thus, it becomes difficult to isolate the strength of an individual muscle. Additionally, differences in the type of exercise assessment administered (e.g., isometric, isokinetic, isotonic, dynamic, single-joint, and multi-joint, etc.) will result in different strength values, diminishing the predictive ability of relative strength measures. In this regard, Wheeler et al. (2014) used a specialized statistical approach and applied it to studies previously conducted in young and old rats that were subjected to a previous animal RET protocol Murlasits et al., 2006;Baker et al., 2010) and demonstrated that dynamic forces were more robust and specific for representing the occurrence of skeletal muscle adaptation compared to isometric values.
The examination of muscle composition may provide additional insight into MQ which can circumvent some of the limitations associated with muscle strength measures. The Bergstrom needle biopsy technique (Bergstrom, 1975) provides useful information about fiber type distribution, muscle capillarization, intramuscular fat content, and muscle metabolism, which aid in predicting muscle function; however, invasive muscle biopsies may not be appropriate for routine MQ assessment. Advancements in fine needle biopsies techniques allow for a less-invasive immunohistological and morphological analysis of muscle tissue (Townsend et al., 2016), but this method still requires repeated muscle sample collection, which may not be practical for most populations. In contrast, muscle imaging techniques, such as computed tomography (CT), peripheral quantitative computed tomography (pQCT) magnetic resonance imaging (MRI), and ultrasonography (US) serve as non-invasive approaches for assessing muscle size and tissue composition, allowing for surrogate measures of MQ that can be derived independently of muscle strength measures. Previous studies have reported skeletal muscle-based outcome measures using dual x-ray absorptiometry (DXA) in various healthy populations following RET despite the notion that DXA cannot distinguish between muscle mass and MQ (Heymsfield et al., 2015;Phillips et al., 2017). Anthropometric measurements that are commonly used to represent skeletal muscle health, such as skinfolds and circumferences, not only have their own inherent limitations such as poor precision/reproducibility, they provide no information pertaining to the underlying contractile and non-contractile tissue components that influence functional outcomes and account for disconnects between size and force production (Heymsfield et al., 2015). Therefore, muscle imaging may be preferred for MQ assessment when muscle strength measures cannot be obtained or when muscle composition estimates are also desired, as relative strength measures do not provide any information on muscle composition. However, the reliability of MQ measures are dependent on the method of examination. For example, the reliability of echo intensity measured via ultrasonography will be different from that of radiological density measured by MRI, which will be different from that of relative strength. Nevertheless, all methods of assessing MQ mentioned herein have been reported to be reliable across different populations and are widely cited throughout the literature. Advantages and disadvantages of these imaging techniques used to measure MQ are presented in Table 2.
CT produces high-resolution, cross-sectional images of body "slices, " which can be combined to estimate muscle volumes and whole body muscle mass (Heymsfield et al., 2015;Correa-de-Araujo et al., 2020). However, CT is unable to distinguish fibrotic tissue from normal muscle tissue, limiting the ability of CT to provide measures of MQ that exclude impacts of fat infiltration. CT is also unable to isolate individual muscle groups or distinguish the location of intramuscular fat. (Goodpaster, 2002;Machann et al., 2003). Advancements in CT technology have resulted in the development of pQCT machines, which enable 3-dimensional CT scans of the peripheral skeleton. Advantages of pQCT over CT include its lower cost, increased portability and smaller size, shorter scan time, and lower emittance of radiation (Erlandson et al., 2016(Erlandson et al., , 2017. However, pQCT shares some of the same limitations in that it is incapable of isolating individual muscle groups and cannot determine the location of intramuscular fat. MRI is often considered the gold standard method for measuring muscle size and CSA (Ahtiainen et al., 2010) and provides high-resolution images of body tissues, making visualization easy (Pillen and van Alfen, 2011).
MRI is also more sensitive than CT for detecting muscle fat infiltration and visualizing anatomical features (Gloor et al., 2011). Furthermore, MRI assesses the detailed structure and composition of individual muscles and differentiates between edema, fatty infiltration, and fibrosis (Erlandson et al., 2016).
While there is currently no gold standard imaging device to assess MQ, the use of US has become increasingly prevalent in recent research due to the low cost, safety, portability, and reliability as an imaging device. US has recently emerged as one of the most popular ways to assess muscle morphology; like MRI, US does not emit radiation, making it attractive for repeated use. US-derived measures of muscle CSA have demonstrated high reliability and accuracy in comparison to other imaging techniques (Ahtiainen et al., 2010;Noorkoiv et al., 2010;Scott et al., 2012). MQ measures are based off of echo intensity (EI), or brightness, of the tissue in the US image. Thus, muscle with a greater proportion of non-contractile tissue appears brighter in color, accompanied by a higher EI value, and ultimately lower MQ. Several studies report that EI is related to muscle strength, power, and function across the population spectrum, demonstrating that EI may be a proxy measure of MQ (Jajtner et al., 2013;Watanabe et al., 2013;Fragala et al., 2014b;Mangine et al., 2015a;Stock and Thompson, 2020;Wong et al., 2020).

EXERCISE AND MQ
In general, exercise training elicits positive adaptations to MQ. However, as outlined in Table 3, in comparison to other exercise training regimens such as aerobic exercise training or hypertrophy-based moderate intensity resistance exercise, high-intensity RET appears to be the primary intervention for improving force production, power development, and subsequently augmenting MQ as well as overall muscle function, especially when consisting of stretch-shortening contractions (SSCs) (Fry, 2004;Rader and Baker, 2017;Rader et al., 2018a;Szivak, 2020;Duchateau et al., 2021). SSCs consist of sequential isometric, eccentric, and concentric contractions, such as the squat, during which the muscle is activated prior to (isometricthis represents the stabilization phase when holding the bar prior to the descent) as well as during the initial stretch/lengthening (eccentric-the descending portion of the squat) and subsequent shortening (concentric-the ascending portion of the squat) Rader and Baker, 2017;Rader et al., 2017b). SSCs provide a significant advantage over isolated isometric-, concentric-, or eccentric-only contractions because they are more physiologically relevant as the typical contraction sequence utilized by mammals that occur during activities of daily living as well as the majority of exercise movements (e.g., walking, sprinting, resistance training, and plyometrics) (Vaczi et al., 2014;Baker, 2017, 2020;Rader et al., 2018a). As most traditional free-weight RET paradigms incorporate SSCs as part of the typical routine (i.e., most training programs do not isolate a single type of contraction), we will refer to RET using SSCs as "RET" for the remainder of the paper. Common physiological adaptations promoted specifically by a high-intensity RET stimulus (≥70% one-repetition maximum, 1RM) include an augmentation of muscle capillarization, reduced muscle lipid content, increased motor unit recruitment, and a  Reimers et al., 1993;Pillen et al., 2009;Ihnatsenka and Boezaart, 2010;Cadore et al., 2012;Drakonaki et al., 2012;Radaelli et al., 2012;Jajtner et al., 2013Jajtner et al., , 2015Fragala et al., 2014a;Sikdar et al., 2014;Mangine et al., 2015a;Young et al., 2015;Hacker et al., 2016;Arroyo et al., 2018;Watanabe et al., 2018;Varanoske et al., 2019Varanoske et al., , 2020 Frontiers in Physiology | www.frontiersin.org High-intensity RET Has been recommended as the preeminent means for enhancing muscle mass and strength due to its common physiological effects, which include an augmentation of muscle capillarization, reduced muscle lipid content, increased motor unit recruitment, and a selective preferential increase in type II muscle fiber recruitment and size that are elicited by this specific stimulus While proven that it can be done safely and without indices of injury, high-intensity RET may be cautioned against being implemented in specific sectors of the population, such as novice lifters; overreaching may occur as a consequence to high intensity RET if done frequently without adequate recovery time Fry, 2004;American College of Sports Medicine, 2009;Garber et al., 2011;Fisher et al., 2017;Rader et al., 2018a;Abe et al., 2020;Travis et al., 2020;Vann et al., 2020;Duchateau et al., 2021 selective increase in the number of type II muscle fibers that are activated during training, which are able to generate the greatest force output and have the highest capability for growth (Frontera et al., 1988;Hepple et al., 1997;Hagerman et al., 2000;Vaczi et al., 2014;Rader and Baker, 2017;Szivak, 2020). While increases in muscle mass have been reported to occur over a broader range of intensities (American College of Sports Medicine, 2009; Shoepe et al., 2020), preferential increases in type II muscle fiber CSA have been shown specifically through high-intensity training protocols (Fry, 2004;Vann et al., 2020).

MQ AND HIGH-INTENSITY RET IN YOUNG POPULATIONS
Despite the critical importance of MQ in meeting the requirements of physically demanding tasks, a comprehensive summary of the effects of enhanced MQ associated with specific exercise regimens has not focused on younger populations in highly physically demanding occupations, such as the military. Synthesizing this information is highly relevant for making evidence-based recommendations for improving MQ in younger populations who regularly engage in physical tasks where optimizing muscle function is of high importance. Before providing a review of studies, it is important to note that the classification of what is appropriately labeled "high-intensity" appears to be quite ambiguous and often differs between researchers (Steele, 2014;Steele et al., 2017). However, there is a general consensus that, when relating intensity to load, ≥70% of 1RM is the minimum threshold for being considered highintensity (Kristensen and Franklyn-Miller, 2012;Steele, 2014). Therefore, we considered and discussed studies that directly measured MQ where intensity as it relates to load was exclusively or predominantly at ≥ 70% or greater 1RM, while recognizing the limitation of the lack of clarity on a consensus definition. For this review, only studies that utilized SSCs were considered, while those employing isometric, concentric-, or eccentric-only training were excluded given the advantages of this contraction sequence. In addition to these standards, other criteria for inclusion were training studies with a minimum duration of 4 weeks, a minimum training frequency of two times per week, and the requirement that there was at least one metric of skeletal muscle performance/strength and/or muscle mass reported in the study.
Animal-based rodent models have provided an important and fundamental approach to studying MQ responses in young muscle because of the capability to tightly control high-intensity RET paradigms and precisely assess components of MQ. As shown in Table 4, young rats have consistently and robustly responded to an in vivo dynamometer model of SSC-loading with a training-induced adaptation in the tibialis anterior (TA), a muscle predominantly comprised of type II fibers (>90%) (Delp and Pette, 1994). This adaptive response is reflected by a ∼15-100% increase in isometric and dynamic skeletal muscle performance as well as a roughly ∼10-25% increase in TA muscle wet-weight, depending on the specific metric utilized and selected method of quantification, ultimately resulting in a robust enhancement of MQ. Additionally, young mice subjected to the same model and training protocol to the plantar flexor muscles responded with a ∼20% increase in dynamic skeletal muscle performance, but with no change in plantaris muscle mass. The other primary model included in Table 4 was a recently developed custom-built voluntary weightlifting apparatus designed for mice to perform squat-like activities against an adjustable load during feeding (Cui et al., 2020). Using this model, substantial increases in plantar flexor contractile force, muscle CSA, and MQ (plantar flexor torque forces normalized to muscle mass) were observed.
Besides the summary of the results for MQ provided in Table 4, a key observation regarding fiber type distribution has been that young rats (3 month old) have demonstrated a transition to a more oxidative phenotype with high-intensity RET, either from type IIb to IIx (Rader et al., 2016(Rader et al., , 2017a or type IIx to IIa (Aguiar et al., 2013). Also, with respect to adult skeletal muscle, results from a study (Rader et al., 2016) indicated there was an altered phenotype occurring prior to complete biological development of rodents, which generally occurs by 6 months of age, or young adulthood. This was highlighted by impairments in the adaptive capacity due to a blunted MQ response following the same high-intensity RET protocol in comparison to 3-month-old rats who had markedly increased MQ (Cooper et al., 2015;Rader et al., 2016). These results indicate that skeletal muscle can potentially experience declines in its ability to adapt with age, including at the onset of young adulthood. These outcomes, should they hold true for humans, have important implications for young adult military personnel who are still expected to perform at high levels of function during physically demanding tasks.
The effects of high-intensity RET (>70% 1RM) on MQ, as defined by muscle strength relative to mass, has been investigated in young, healthy human populations (Table 5). Collectively, following high-intensity RET, all but one of these studies showed significant improvements in muscle strength/performance (∼4-75%), and all seven studies showed increases in muscle mass (∼4-35%). Ultimately, these studies had an overall ∼8.5-35.0% increase in MQ following RET. Of these studies, four used untrained participants (Cureton et al., 1988;Chestnut and Docherty, 1999;Ivey et al., 2000) and in two others, training status was not reported (Dons et al., 1979;Welle et al., 1996). It is important to acknowledge that untrained individuals respond differently to RET than trained individuals. In the reviewed studies, untrained individuals respond positively to the vast majority of RET programs, and thus specific nuances to the exercise prescription are less critical (Aagaard and Andersen, 1998). Castro et al. (1995) found trained participants had significantly greater mean torque per unit of muscle and bone CSA for the upper arm (28.9%) and thigh (18.8%) compared to untrained participants following RET (Castro et al., 1995), indicating that trained participants potentially have greater capabilities to augment MQ in response to high-intensity RET. Two of the aforementioned studies made direct comparisons between different RET intensities. One study found MQ to be 30% higher at post-training in a group that trained at 80% 1RM, whereas there was only a 5% increase in post-training MQ in a 50% 1RM group (Dons et al., 1979). In the other study, there were no changes in MQ between 4RM vs. 10RM group (Cureton et al., 1988). However, since both groups trained at relatively high intensities of 85% and 70% 1RM, respectively, along with the lack of other available direct comparisons, it is difficult to draw any conclusions on the effects of specific intensities on MQ in young populations following high-intensity RET.
Given that published research provides support that highintensity RET improves muscle strength, mass, and composition in young individuals, proxy measures of MQ assessed with imaging techniques such as EI measured via US would also be expected to demonstrate this MQ improvement. However, a majority of the research demonstrating that exercise interventions increase MQ as reflected by a decrease in muscle EI have been conducted in older adults or diseased populations (Radaelli et al., 2013Cadore et al., 2014;Wilhelm et al., 2014;Yoshiko et al., 2017Yoshiko et al., , 2018Yamada et al., 2019). Few investigations have examined the impact of RET on EI in young individuals, making it difficult to make definitive conclusions. Nevertheless, studies examining the effects of high-intensity RET on EI in younger populations listed in Table 6 demonstrate comparable training-induced improvements in muscle performance and/or mass to those in Table 5. Furthermore, the majority of these studies showed enhanced MQ (i.e., decreased EI of ∼5-16%) following highintensity RET. However, two of the aforementioned studies, despite showing increased muscle performance (∼4-22%) and size (∼3-7%), did not report changes in MQ (Wells et al., 2014;Jenkins et al., 2016). A number of factors related to US measurement could have affected the results, such as probe placement, muscle depth, subcutaneous adipose tissue thickness, and patient positioning (Young et al., 2015;Dankel et al., 2018;Varanoske et al., 2019). Of these studies, three performed direct comparisons between high and low intensity training and showed that high-intensity training resulted in greater post-training relative increases in muscle performance and hypertrophy, with two of the three also reporting greater decreases in EI (higher improvements in MQ) in the high-intensity group (Jenkins et al., 2017;Ikezoe et al., 2020). Taken together, these findings demonstrate that RET in young individuals may improve MQ as assessed via ultrasonography.
Additional evidence demonstrates that the components of muscle adaptation that MQ is derived from (i.e., force to size ratio) is noticeably improved by high-intensity RET. In a recent No differences for MQ between 2 or 3 day/wk training; chi-square analysis of muscle mass fiber size area distributions showed an ↑ at both frequencies Rader et al. (2018a) 3 month old male FBN rats (n = 9-10 per group) Same as Cutlip et al. (2006) Maximal RET of the dorsiflexor muscles 3 days/wk. for 4.5 wks., 4 sets of one isometric repetition (4 total) or 4 sets of 10 SSCs (40 total), 2 min rest between sets ↑ peak force at final vs. initial for both 4 isometric contractions (20.1%) or 40 SSCs (16.5%); ↑ isometric peak force at final vs. initial for both 4 isometric contractions (13.9%) or 40 SSCs (8.0%; p = 0.097) ↑ TA muscle mass normalized to tibia length in loaded vs. NLC muscle for both 4 isometric contractions (7.0 ± 2.0%) and 40 SSCs (17.0% ± 2.0%); ↑ (∼8.3%) b TA muscle mass normalized to tibia length of the loaded muscles of 40 SSCs vs. 4 isometric contractions ↑ maximum isometric force divided by normalized muscle mass (i.e., muscle wet weight divided by tibia length) in loaded TA of both 40 SSCs and 4 isometric contractions (0.58 ± 0.03 N/mg/mm and 0.65 ± 0.02 N/mg/mm, respectively) Rader et al. (2018b) 3 month old male Snell dwarf mice and age-matched normal-sized littermate CONs c In vivo dual mode muscle lever system that allows measurement of torque and control of foot rotation about the ankle Maximal training of the plantar flexor muscles 3 days/wk. for 4.5 wks., 8 sets of 10 SSCs (80 total), 2 min rest between sets; ↑ (20.0%) plantarflexion peak muscle torque and maximum isometric torque in loaded vs. NLC muscle ↔ in GTN normalized muscle mass (i.e., muscle wet weight divided by tibia length) or normalized muscle mass per gram of BW      (Lasevicius et al., 2018), the authors found following 12 weeks RET that the highest intensity group (80% 1RM) demonstrated superior increases in muscle strength and CSA in comparison to low intensities. Mangine et al. (2015b) found in response to their 8 week moderate or high-intensity RET program, both groups responded with significant increases in bench press and back squat 1RM strength; however, the highintensity group that trained at 90% of 1RM also had significantly higher bench press 1RM compared to the moderate group. However, not all studies have shown positive effects of highintensity training on MQ. For example, a previous investigation used data questionnaires in college-aged males and females, and based on answers about previous training history, assigned individuals to either a low-or high-intensity resistance training group and subsequently performed a battery of tests looking at muscle function (Shoepe et al., 2020). The high-intensity group had significantly greater handgrip strength but both groups had lower MQ compared to individuals with no history of RET. However, there were several limitations; the study design was retrospective in nature as the authors relied on participant questionnaire responses for group assignments, so an inherent self-bias could have led to inaccurate answers and group placement. Additionally, due to the retrospective design, the exercise intervention conducted was not under the supervision of the investigators; previous research has shown larger effects in strength when RET is supervised (Mazzetti et al., 2000;Lacroix et al., 2017). Finally, the authors chose handgrip strength as a surrogate measure of total body strength. Previous research has shown that handgrip strength is not the best indicator of physical performance (Abe et al., 2016) and that applying 1RM would have been a more representative outcome metric in calculating MQ. In another study by Nóbrega and colleagues (Nobrega et al., 2018), young men (average age: 23.0 years old) participated in two days per week of unilateral leg extension RET for 12 weeks at 30% and 80% 1RM. Following both 6 (midpoint) and 12 weeks (post-training) of exercise, similar improvements in 1RM muscle strength, muscle CSA, and pennation angle were observed. However, training was done using a unilateral leg extension machine (3 sets total per training session), so perhaps the magnitude of the results in the high-intensity groups were hampered by the fact that participants were not performing full body RET with free weights and with overall low session training volume. As noted earlier, a benefit of high-intensity RET is the ability to maximally recruit the majority or all the fibers of a targeted muscle group (Rader et al., 2017b), which is somewhat offset using machines. Although some previous research has demonstrated that short-term (8-week) RET training with free weights or machines induces similar increases in muscle mass and strength (Schwanbeck et al., 2020), free weight usage has resulted in greater electromyography muscle activation (McCaw and Friday, 1994;Schwanbeck et al., 2009), and greater increases in circulating testosterone concentrations (Schwanbeck et al., 2020) than RET using machines. As most improvements in muscle strength during the first phases of training are due to neural adaptations rather than muscle hypertrophy (Moritani and deVries, 1979;Sale, 1988), it is not surprising that increases in muscle mass during short-term RET are similar with free weights and machines (Schwanbeck et al., 2020). However, the greater anabolic response and neural activation observed with free weight RET provide promising evidence that increases in strength and/or hypertrophy may be greater when using free weight RET than machines during longer-term training regimens. Collectively, these studies provide evidence strongly supporting the notion that high-intensity RET, in comparison to other exercise-based interventions, is the most effective exercise strategy for the augmentation of force production, relevant muscle mass, power development, and, ultimately, MQ.

CONCLUSION
While most practical measurement techniques will not capture all of the complex adaptations of muscle to an exercise training stimulus, measurements that account for MQ ultimately reflect the functional summation of complex physiologic changes in response to adaptations to training. MQ has historically been evaluated in older adult and/or clinical populations. However, the paradigm shift observed in the field of aging, to include a focus on MQ rather than a mere loss of muscle mass, has not been replicated to the same degree in young populations. Thus, we reviewed the importance of this measurement in young, healthy adults and highlighted studies that have emphasized the importance of MQ in this cohort.
The collective results from the literature in animals and humans that have utilized physiologically relevant exercise models indicate that high-intensity RET, compared to other exercise training regimens, has the most robust positive effects on augmenting MQ. Younger individuals engaged in intense physical tasks do not simply need to acquire large amounts of muscle mass, but would benefit from increased functional capacity in order to successfully complete their duties. Hence, we put forth the assertion that MQ should be recognized as one of the most important biomarkers for performance enhancement in young individuals. Accordingly, focusing on evidence-based exercise interventions that serve to further enhance MQ in various young populations, such as high-intensity RET, will ultimately improve the capabilities of these individuals to optimally perform the critical responsibilities related to their physically demanding occupational tasks.