Muscle Composition as a Novel Prognostic Tool for Pain, Frailty, and Sarcopenia.

Background and Objective: Skeletal muscle is critical for overall health and predicts quality of life in several chronic diseases, thus quantification of muscle mass and composition is necessary to understand how interventions promote changes in muscle quality. The purpose of this investigation was to quantify changes in muscle mass and composition in two distinct pre-clinical models of changes in muscle quality using a clinical dual X-ray absorptiometry (DEXA), validated for use in mice. Materials and Methods: Adult C57Bl6 male mice were given running wheels (RUN; muscle hypertrophy) or placed in hypobaric hypoxia (HH; muscle atrophy) for four weeks. Animals received weekly DEXA and terminal collection of muscle hind limb complex (HLC) and quadriceps weights and signaling for molecular regulators of muscle mass and composition. Results: HH decreased total HLC muscle mass with no changes in muscle composition. RUN induced loss of fat mass in both the quadriceps and HLC. Molecular mediators of atrophy were upregulated in HH while stimulators of muscle growth were higher in RUN. These changes in muscle mass and composition were quantified by a clinical DEXA, which we described and validated for use in pre-clinical models. Conclusions: RUN improves muscle composition while HH promotes muscle atrophy, though changes in composition in hypoxia remain unclear. Use of the widely available clinical DEXA for use in mice enhances translational research capacity to understand the mechanisms by which atrophy and hypertrophy promote skeletal muscle and overall health.

BackgroundA small cross sectional area (CSA) of the paraspinal muscles may be related to low back pain among military aviators but previous studies have mainly concentrated on spinal disc degeneration. Therefore, the primary aim of the study was to investigate the changes in muscle CSA and composition of the psoas and paraspinal muscles during a 5-year follow up among Finnish Air Force (FINAF) fighter pilots.MethodsStudy population consisted of 26 volunteered FINAF male fighter pilots (age: 20.6 (±0.6) at the baseline). The magnetic resonance imaging (MRI) examinations were collected at baseline and after 5 years of follow-up. CSA and composition of the paraspinal and psoas muscles were obtained at the levels of 3–4 and 4–5 lumbar spine. Maximal isometric strength tests were only performed on one occasion at baseline.ResultsThe follow-up comparisons indicated that the mean CSA of the paraspinal muscles increased (p < 0.01) by 8% at L3–4 level and 7% at L4–5 level during the 5-year period. There was no change in muscle composition during the follow-up period. The paraspinal and psoas muscles’ CSA was positively related to overall maximal isometric strength at the baseline. However, there was no association between LBP and muscle composition or CSA.ConclusionsThe paraspinal muscles’ CSA increased among FINAF fighter pilots during the first 5 years of service. This might be explained by physically demanding work and regular physical activity. However, no associations between muscle composition or CSA and low back pain (LBP) experienced were observed after the five-year follow-up.

While the simultaneous degradation of muscle composition and postural stability in aging are independently highly investigated due to their association with fall risk, the interplay between the two has received little attention. Thus, the purpose of this study is to explore how age-related changes in muscle composition relate to postural stability. To that aim, we collected posturography measures and ultrasound images of the dominant Vastus Lateralis and Biceps Brachii from 32 young (18–35 year old) and 34 older (65–85 year old) participants. Muscle properties were quantified with echo-intensity and texture-based metrics derived from gray-level co-occurrence matrix analysis, and postural stability with the variability of the center of pressure during bipedal stance tasks. Ultrasound parameters revealed that young muscle possessed lower echo-intensity and higher homogeneity compared to the elderly. Echo-intensity and muscle thickness, and several texture-based parameters possessed outstanding young versus older classification performance. A canonical correlation analysis demonstrated a significant relationship between ultrasound and postural measures only within the young group (r = 0.53, p < 0.002), where those with ‘better’ muscle composition displayed larger postural sways. Our results indicate that, in older individuals, postural stability and muscle composition, two common fall risk factors, are unrelated. In view of this decoupling, both may contribute independently to fall risk. Furthermore, our data support the view that texture-based parameters provide a robust alternative to echo-intensity in providing markers of muscle composition.

The ability to safely maintain mobility function with aging is critical as immobility and falls are among the top reasons for long-term care admissions. One potential cause for these functional deficits are muscle composition changes resulting in reductions in muscle mass, strength and power, ultimately contributing to the development of frailty. While the majority of work examining muscle composition and mobility changes with aging have focused on the quadriceps and ankle plantarflexor/dorsiflexor muscles, accumulating evidence suggests that deficits involving the proximal hip muscles may be particularly harmful to balance and mobility functions leading to falls, hip fractures, and frailty. We will discuss muscle changes that occur with aging and frailty, the implications on mobility, and the effects of potential exercise interventions on muscle structure and function as well as their ability to improve functional mobility.

ABSTRACTSkeletal muscle wasting has gained interest as a primary consequence of chronic kidney disease (CKD) due to the relationship between skeletal muscle mass, mortality and major adverse cardiovascular events in this population. The combination of reductions in physical function, skeletal muscle performance and skeletal muscle mass places individuals with CKD at greater risk of sarcopenia. Therefore the monitoring of skeletal muscle composition and function may provide clinical insight into disease progression. Dual-energy X-ray absorptiometry and bioelectrical impedance analysis are frequently used to estimate body composition in people with CKD within clinical research environments, however, their translation into clinical practice has been limited. Proxy measures of skeletal muscle quality can be obtained using diagnostic ultrasound, providing a cost-effective and accessible imaging modality to aid further clinical research regarding changes in muscle composition. Clinicians and practitioners should evaluate the strengths and limitations of the available technology to determine which devices are most appropriate given their respective circumstances. Progressive resistance exercise has been shown to improve skeletal muscle hypertrophy of the lower extremities, muscular strength and health-related quality of life in end-stage renal disease, with limited evidence available in CKD predialysis. Fundamental principles (i.e. specificity, overload, variation, reversibility, individuality) can be used in the development of more advanced programs focused on improving specific neuromuscular and functional outcomes. Future research is needed to determine the applicability of skeletal muscle monitoring in clinical settings and the feasibility and efficacy of more advanced resistance exercise approaches in those with CKD predialysis.

Loss of skeletal muscle strength is a well-recognized feature of ageing and chronic obstructive pulmonary disease (COPD). Reductions in muscle size provide only a partial explanation for this loss of strength, and additional contributory factors remain undetermined. We hypothesized that reductions in skeletal muscle strength, as measured in the ankle dorsiflexor muscles, would be reduced with ageing and COPD as a result of changes in both size and composition of the tibialis anterior muscle. Twenty healthy young subjects, 18 healthy elderly subjects and 17 patients with COPD were studied. Ankle dorsiflexor muscle strength was assessed by maximal voluntary contraction (ADMVC) and 100 Hz supramaximal electrical stimulation of the peroneal nerve (100 HzAD). Tibialis anterior cross-sectional area (TACSA) and composition, as assessed by echo intensity (TAEI), were measured using ultrasonography. Despite a lack of differences in TACSA between groups, ADMVC and 100 HzAD were significantly reduced in COPD patients compared with both healthy elderly and healthy young subjects, when expressed as absolute values and when normalized to TACSA (P < 0.01). The TAEI was, however, higher in COPD patients compared with healthy elderly (P = 0.025) and healthy young subjects (P = 0.0008), suggesting increased levels of non-contractile tissue. Across all participants, ADMVC and 100 HzAD correlated positively with TACSA (r = 0.78, P < 0.0001) and negatively with TAEI (r = -0.46, P < 0.0005). The variance in 100 HzAD was best explained with a regression model incorporating TACSA, TAEI, age and COPD status (r(2) = 0.822, P = 0.001). These data demonstrate that the loss of skeletal muscle strength in COPD is related to changes in muscle composition, with infiltration of non-contractile tissue beyond that seen during normal ageing.

Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial.

Spinal cord injury (SCI) results in skeletal muscle atrophy, increases in intramuscular fat, and reductions in skeletal muscle oxidative capacity. Endurance training elicited with neuromuscular electrical stimulation (NMES) may reverse these changes and lead to improvement in muscle metabolic health. Fourteen participants with complete SCI performed 16 weeks of home-based endurance NMES training of knee extensor muscles. Skeletal muscle oxidative capacity, muscle composition, and blood metabolic and lipid profiles were assessed pre- and post-training. There was an increase in number of contractions performed throughout the duration of training. The average improvement in skeletal muscle oxidative capacity was 119%, ranging from -14% to 387% (P = 0.019). There were no changes in muscle composition or blood metabolic and lipid profiles. Endurance training improved skeletal muscle oxidative capacity, but endurance NMES of knee extensor muscles did not change blood metabolic and lipid profiles. Muscle Nerve 55: 669-675, 2017.

Computed tomography (CT) can yield quantitative imaging data from detailed maps of linear attenuation coefficients within tissue. The attenuation characteristics of skeletal muscle and adipose tissue can be quantified in vivo to provide information about the composition of skeletal muscle and the distribution of adipose tissue within muscle. Several studies have taken advantage of this utility to quantify skeletal muscle composition and fatty infiltration of muscle, in particular to quantify the attenuation characteristics of muscle as a marker of its lipid content. In this manner we found that the mean muscle attenuation of skeletal muscle reflects an increase in its fat content in obesity, and that this regional body composition parameter is strongly related to insulin-resistant glucose metabolism. In addition, muscle composition and adipose tissue distribution within muscle may be altered with clinical weight-loss interventions. CT may also provide important information about the changes in muscle mass and composition with aging and disease, which may, in turn, affect the muscle's function. In summary, CT can provide important quantitative data on the composition of muscle, and the distribution of adipose tissue within it, and this may be important in examining the relationships among skeletal muscle metabolism, lipid accumulation within muscle, and muscle function.

Hoplias malabaricus (traíra) were experimentally starved (0 to 240 days) and subsequently re-fed for 30 days (after 90 and 240-d fasting). Long-term starvation produced minor changes in muscle composition, but shrinkage of muscle fibres was a conspicuous result. The diameter of muscle fibres decreased gradually and the spaces among them increased as the starvation period progressed. After re-feeding, fish prior starved for 90 days presented partial restoration on diameter of muscle fibres. However, the fibres remained shrunken after re-feeding following 240-d fasting. While the lipid content did not change, the protein levels fell after 240-d fasting, but they were restored after re-feeding

Age-related changes in muscle composition and function are often treated using exercise, including muscles of the tongue to treat swallowing impairments (dysphagia). Although tongue exercise is commonly prescribed, optimal tongue exercise doses have not been determined. The purpose of this study was to evaluate effects of varying tongue exercise frequency on tongue force, genioglossus muscle fiber size, composition and metabolism, and swallowing in a rat model. We randomized 41 old and 40 young adult Fischer 344/Brown Norway rats into one of four tongue exercise groups: 5days/week; 3days/week; 1day/week; or sham. Tongue force was higher following all exercise conditions (vs sham); the 5day/week group had the greatest change in tongue force (p < 0.001). There were no exercise effects on genioglossus (GG) fiber size or MyHC composition (p > 0.05). Significant main effects for age showed a greater proportion of Type I fibers in (p < 0.0001) and increased fiber size of IIa fibers (p = 0.026) in old. There were no significant effects of citrate synthase activity or PGC-1α expression. Significant differences were found in bolus speed and area (size), but findings were potentially influenced by variability. Our findings suggest that tongue force is influenced by exercise frequency; however, these changes were not reflected in characteristics of the GG muscle assayed in this study. Informed by findings of this study, future work in tongue dose optimization will be required to provide better scientific premise for clinical treatments in humans.

Recent years have seen tremendous progress towards therapy of many previously incurable neuromuscular diseases. This new context has acted as a driving force for the development of novel non-invasive outcome measures. These can be organized in three main categories: functional tools, fluid biomarkers and imagery. In the latest category, nuclear magnetic resonance imaging (NMRI) offers a considerable range of possibilities for the characterization of skeletal muscle composition, function and metabolism. Nowadays, three NMR outcome measures are frequently integrated in clinical research protocols. They are: 1/ the muscle cross sectional area or volume, 2/ the percentage of intramuscular fat and 3/ the muscle water T2, which quantity muscle trophicity, chronic fatty degenerative changes and oedema (or more broadly, “disease activity”), respectively. A fourth biomarker, the contractile tissue volume is easily derived from the first two ones. The fat fraction maps most often acquired with Dixon sequences have proven their capability to detect small changes in muscle composition and have repeatedly shown superior sensitivity over standard functional evaluation. This outcome measure will more than likely be the first of the series to be validated as an endpoint by regulatory agencies. The versatility of contrast generated by NMR has opened many additional possibilities for characterization of the skeletal muscle and will result in the proposal of more NMR biomarkers. Ultra-short TE (UTE) sequences, late gadolinium enhancement and NMR elastography are being investigated as candidates to evaluate skeletal muscle interstitial fibrosis. Many options exist to measure muscle perfusion and oxygenation by NMR. Diffusion NMR as well as texture analysis algorithms could generate complementary information on muscle organization at microscopic and mesoscopic scales, respectively. 31P NMR spectroscopy is the reference technique to assess muscle energetics non-invasively during and after exercise. In dystrophic muscle, 31P NMR spectrum at rest is profoundly perturbed, and several resonances inform on cell membrane integrity. Considerable efforts are being directed towards acceleration of image acquisitions using a variety of approaches, from the extraction of fat content and water T2 maps from one single acquisition to partial matrices acquisition schemes. Spectacular decreases in examination time are expected in the near future. They will reinforce the attractiveness of NMR outcome measures and will further facilitate their integration in clinical research trials.

Constancy of masseter muscle structure and function with age in F344 rats

ObjectiveThis study investigated morphological changes in the composition of the pelvic floor muscles, degree of atrophy, and urethral function in a rat of simulated birth trauma induced by vaginal distension (VD) model.MethodsFemale Sprague–Dawley rats were classified into four groups: a sham group, and 1, 2, and 4 weeks post-VD (1 W, 2 W, and 4 W, respectively) groups. We measured the amplitude of urethral response to electrical stimulation (A-URE) to evaluate urethral function. After measuring the muscle wet weight of the pubococcygeus (Pcm) and iliococcygeus (Icm) muscles, histochemical staining was used to classify muscle fibers into Types I, IIa, and IIb, and the occupancy and cross-sectional area of each muscle fiber were determined.ResultsThere were 24 Sprague–Dawley rats used. A-URE was significantly lower in the 1 W group versus the other groups. Muscle wet weight was significantly lower in the VD groups versus the sham group for Pcm. The cross-sectional area of Type I Pcm and Icm was significantly lower in the VD groups versus the sham group. Type I muscle fiber composition in Pcm was significantly lower in the VD groups versus the sham groupand lowest in the 2 W group. Type I muscle fiber composition in Icm was significantly lower in the 2 and 4 W groups versus the sham group.ConclusionMuscle atrophy and changes in muscle composition in the pelvic floor muscles were observed even after improvements in urethral function. These results may provide insight into the pathogenesis of stress urinary incontinence after VD.

Age-related increases in intermuscular adipose tissue (IMAT) impair muscle quality, decrease functional capacity, and promote several cardiometabolic and inflammatory disorders. Whether these age-related alterations in muscle composition improve by consuming a high-protein (HP) diet with whole eggs are unclear. This parallel-design, randomized-controlled trial assessed the effects of a 12-week eucaloric HP diet with three whole eggs per day (1.4 g protein kg−1 day−1) versus a normal-protein diet void of eggs (NP, 0.8 g protein kg−1 day−1) on muscle composition (IMAT), cardiometabolic health, and systemic inflammation in older adults with overweight or obesity (12 men and 10 women; age 70 ± 5 years, BMI 31.3 ± 3.2 kg/m2, mean ± SD). No changes in muscle composition were observed over time, independent of protein intake. Total body weight was reduced in both groups (−3.3 ± 1.2%) and lean mass was preserved only with the HP diet. LDL concentration and hip circumference decreased only with the NP diet, while MCP-1 and HsCRP concentrations increased over time in both groups. A HP diet with whole eggs promotes lean mass retention with modest weight loss, but does not positively influence muscle composition, cardiometabolic health or systemic inflammation, compared to a NP diet void of eggs.