Human skeletal muscle disuse atrophy: effects on muscle protein synthesis, breakdown and insulin resistance- a qualitative review

The ever increasing burden of an ageing population and pandemic of metabolic syndrome worldwide demands further understanding of the modifiable risk factors in reducing disability and morbidity associated with these conditions. Disuse skeletal muscle atrophy (sometimes referred to as “simple” atrophy) and insulin resistance are ‘non-pathological’ events resulting from sedentary behaviour and periods of enforced immobilization e.g. due to fractures or elective orthopaedic surgery. Yet, the processes and drivers regulating disuse atrophy and insulin resistance and the associated molecular events remain unclear – especially in humans. The aim of this review is to present current knowledge of relationships between muscle protein turnover, insulin resistance and muscle atrophy during disuse, principally in humans. Immobilisation lowers fasted state muscle protein synthesis (MPS) and induces fed-state ‘anabolic resistance’. While a lack of dynamic measurements of muscle protein breakdown (MPB) precludes defining a definitive role for MPB in disuse atrophy, some proteolytic “marker” studies (e.g. MPB genes) suggest a potential early elevation. Immobilisation also induces muscle insulin resistance (IR). Moreover, the trajectory of muscle atrophy appears to be accelerated in persistent IR states (e.g. Type II diabetes), suggesting IR may contribute to muscle disuse atrophy under these conditions. Nonetheless, the role of differences in insulin sensitivity across distinct muscle groups and its effects on rates of atrophy remains unclear. Multifaceted time-course studies into the collective role of insulin resistance and muscle protein turnover in the setting of disuse muscle atrophy, in humans, are needed to facilitate the development of appropriate countermeasures and efficacious rehabilitation protocol

Estimation of changes in volume of individual lower-limb muscles using magnetic resonance imaging (during bed-rest)

Muscle size in the lower limb is commonly assessed in neuromuscular research as it correlates with muscle function and some approaches have been assessed for their ability to provide valid estimates of muscle volume. Work to date has not examined the ability of different measurement approaches (such as cross-sectional area (CSA) measures on magnetic resonance (MR) imaging) to accurately track changes in muscle volume as a result of an intervention, such as exercise, injury or disuse. Here we assess whether (a) the percentage change in muscle CSA in 17 lower-limb muscles during 56 days bed-rest, as assessed by five different algorithms, lies within 0.5% of the muscle volume change and (b) the variability of the outcome measure is comparable to that of muscle volume. We find that an approach selecting the MR image with the highest muscle CSA and then a series of CSA measures, the number of which depended upon the muscle considered, immediately distal and proximal, provided an acceptable estimate of the muscle volume change. In the vastii, peroneal, sartorius and anterior tibial muscle groups, accurate results can be attained by increasing the spacing between CSA measures, thus reducing the total number of MR images and hence the measurement time. In the two heads of biceps femoris, semimembranosus and gracilis, it is not possible to reduce the number of CSA measures and the entire muscle volume must be evaluated. Using these approaches one can reduce the number of CSA measures required to estimate changes in muscle volume by â¼60%. These findings help to attain more efficient means to track muscle volume changes in interventional studies

Muskel Atrophie der postero-lateralen Hüft- und Beinmuskulatur und die Wirksamkeit von zwei verschiedenen Gegenmaßnahmen mit der Verhinderung von Muskelschwund bei längerer Bettruhe

As part of the Berlin Bed Rest Study (BBR) and 2nd Berlin Bed Rest Study (BBR2-2), this work investigated the pattern of muscle atrophy of the postero- lateral hip and lower limb musculature during prolonged bed-rest and the effectiveness of two different exercise countermeasures- resistive exercise alone and resistive exercise with whole body vibration, in preventing muscle atrophy. For the BBR, 20 healthy male subjects underwent 56 days of horizontal bed-rest and were assigned to either an inactive control group (CTR) or resistive vibration exercise group (VRE). For BBR2-2, 24 healthy male subjects underwent 60 days of 6 degrees head-down-tilt (HDT) bed-rest and were assigned to a control group (CTR), resistive vibration exercise group (RVE) or resistive exercise alone group (RE). Magentic resonance imaging (MRI) of the hip and thigh were taken prior to, during and at the end of bed-rest. Volume of the postero-lateral hip and lower limb musculature were calculated and the rate of muscle atrophy and the effect of countermeasure exercises examined. During bed-rest, the CTR group demonstrated differential rates of muscle volume loss (p<0.0001). The fastest rates of atrophy were seen in the triceps surae (medial gastrocnemius, lateral gastrocnemius, soleus), mono-articular knee extensors (vastii), mono-articular hip extensors and quadratus femoris, an external rotator of the hip and the hamstring muscles. The other postero- medial and postero-lateral muscles of the foot/ankle in addition to the adductor magnus were also strongly affected during bed-rest. The antero-medial hip muscles and anterior tibial muscles were comparatively less affected by bed-rest. Different rates of atrophy were also seen amongst some muscle synergists. For example, the heads of triceps surae and heads of the hamstring muscle group demonstrated different rates of atrophy, the vastii demonstrated a faster rate of atrophy than rectus femoris and upper gluteus maximus atrophied faster than lower gluteus maximus and gluteus medius. Countermeasure exercise reduced/prevented muscle atrophy in the triceps surae, vastii and gluteal muscles but was less effective for the hamstring muscles, postero- medial and postero-lateral muscles of the foot/ankle and the adductor muscles. The addition of whole body vibration to resistive exercise did not have an additional effect for the variables examined in this work. In conclusion, a short-duration resistive exercise program with or without whole-body vibration can be effective in reducing the impact of prolonged bed-rest on postero- lateral hip and lower extremity muscle volume loss during bed-rest.Als Teil der Berlin Bed Rest Study (BBR) und 2. Berlin Bed Rest Study (BBR2-2), wurden die Charakteristika der Muskel Atrophie der postero-lateralen Hüft -und Beinmuskulatur untersucht. Außerdem, wurde die Wirksamkeit von zwei verschiedenen Gegenmaßnahmen - Widerstandstraining alleine und Widerstandstraining mit Ganzkörpervibration, bei der Verhinderung von Muskelschwund bei längerer Bettruhe, untersucht. Für die BBR-Studie, wurden 20 gesunde männliche Probanden 56 Tage in horizontaler Bettruhe entweder einer inaktiven Kontrollgruppe (CTR) oder einer Widerstands- vibrationstrainingsgruppe (VRE) zugeordnet. Für BBR2-2, wurden 24 gesunde männliche Probanden 60 Tage, in 6 Grad Kopftieflage (Head-down-tilt = HDT) einer Kontrollgruppe (CTR-Gruppe), einer Widerstandstrainingsgruppe (RE) oder einer Widerstand-Vibrationstrainingsgruppe (RVE) zugeordnet. Das Muskelvolumen der postero-lateralen Hüft- und Beinmuskulatur wurde mit MRT-Untersuchungen dargestellt und die Geschwindigkeiten der Muskelatrophie und die Wirkung der Gegenmaßnahmen berechnet. Die Geschwindigkeiten der Muskelatrophie Entwicklung der postero-laterale Hüft- und Beinmuskulatur waren unterschiedlich (p<0.0001). Die größte Atrophie fand sich beim Triceps surae (Medialer gastrocnemius, Lateraler gastrocnemius, Soleus), den Kniestreckern (Vastii), bei den Hüftextensoren, dem Quadratus femoris, einem Muskel, der die Hüfte nach außen dreht, und den Oberschenkelmuskeln. Die anderen postero-medialen und postero-lateralen Muskeln des Fußes/Knöchel und der Adduktor wurden während der Bettruhe auch stark betroffen. Die antero-mediale Hüftmuskulatur und der vorderen Schienbeinmuskeln waren vergleichsweise wenig während der Bettruhe betroffen. Unterschiedliche Atrophie-Geschwindigkeiten wurden auch zwischen synergistische Muskeln gesehen. Die verschiedenen Köpfe der Triceps surae und hinteren Oberschenkel Muskel-Gruppe demonstrierte unterschiedliche Geschwindigkeiten der Atrophie; die Vastii wiesen eine schnellere Geschwindigkeit der Atrophie auf als der Rectus femoris; die oberen Gesäßmuskeln wiesen eine schnellere Geschwindigkeit der Atrophie auf als der untere Gesäßmuskel und der Gluteus medius. Zusammenfassend vermindern die Gegenmaßnahmen die Muskelatrophie im Triceps surae, in den Vastii und in der Gesäßmuskulatur, waren aber weniger wirksam für die hinteren Oberschenkelmuskeln, die postero-mediale und postero-laterale Muskeln des Fußes / Knöchel und der Adduktoren während längerer Bettruhe. Die zusätzliche Ganzkörpervibration beim Widerstandstraining hat keinen zusätzlichen Effekt auf die untersuchten Muskelgruppen

Evaluation of neck muscle size: long-term reliability and comparison of methods

Although it is important for prospective studies, the reliability of quantitative measures of cervical muscle size on magnetic resonance imaging is not well established. The aim of the current work was to assess the long-term reliability of measurements of cervical muscle size. In addition, we examined the utility of selecting specific sub-regions of muscles at each vertebral level, averaging between sides of the body, and pooling muscles into larger groups. Axial scans from the base of skull to the third thoracic vertebra were performed in 20 healthy male subjects at baseline and 1.5&thinsp;years later. We evaluated the semi-spinalis capitis, splenius capitis, spinalis cervicis, longus capitis, longus colli, levator scapulae, sternocleidomastoid, anterior scalenes and middle with posterior scalenes. Bland-Altman analysis showed all measurements to be repeatable between testing-days. Reliability was typically best when entire muscle volume was measured (co-efficients of variation (CVs): 3.3-8.1% depending on muscle). However, when the size of the muscle was assessed at specific vertebral levels, similar measurement precision was achieved (CVs: 2.7-7.6%). A median of 4-6 images were measured at the specific vertebral levels versus 18-37 images for entire muscle volume. This would represent considerable time saving. Based on the findings we also recommend measuring both sides of the body and calculating an average value. Pooling specific muscles into the deep neck flexors (CV: 3.5%) and neck extensors (CV: 2.7%) can serve to reduce variability further. The results of the current study help to establish outcome measures for interventional studies and for sample size estimation

Differential atrophy of the postero-lateral hip musculature during prolonged bedrest and the influence of exercise countermeasures

As part of the 2nd Berlin BedRest Study (BBR2-2), we investigated the pattern of muscle atrophy of the postero-lateral hip and hamstring musculature during prolonged inactivity and the effectiveness of two exercise countermeasures. Twenty-four male subjects underwent 60 days of head-down tilt bedrest and were assigned to an inactive control (CTR), resistive vibration exercise (RVE), or resistive exercise alone (RE) group. Magnetic resonance imaging (MRI) of the hip and thigh was taken before, during, and at end of bedrest. Volume of posterolateral hip and hamstring musculature was calculated, and the rate of muscle atrophy and the effect of countermeasure exercises were examined. After 60 days of bedrest, the CTR group showed differential rates of muscle volume loss (F = 21.44; P ≤ 0.0001) with fastest losses seen in the semi-membranosus, quadratus femoris and biceps femoris long head followed by the gluteal and remaining hamstring musculature. Whole body vibration did not appear to have an additional effect above resistive exercise in preserving muscle volume. RE and RVE prevented and/or reduced muscle atrophy of the gluteal, semi-membranosus, and biceps femoris long head muscles. Some muscle volumes in the countermeasure groups displayed faster recovery times than the CTR group. Differential atrophy occurred in the postero-lateral hip musculature following a prolonged period of unloading. Short-duration high-load resistive exercise during bedrest reduced muscle atrophy in the mono-articular hip extensors and selected hamstring muscles. Future countermeasure design should consider including isolated resistive hamstring curls to target this muscle group and reduce the potential for development of muscle imbalances

Hypertrophy in the cervical muscles and thoracic discs in bed rest?

The impact of prolonged bed rest on the cervical and upper thoracic spine is unknown. In the 2nd Berlin BedRest Study (BBR2-2), 24 male subjects underwent 60-day bed rest and performed either no exercise, resistive exercise, or resistive exercise with whole body vibration. Subjects were followed for 2 yr after bed rest. On axial cervical magnetic resonance images from the skull to T3, the volumes of the semispinalis capitis, splenius capitis, spinalis cervicis, longus capitis, longus colli, levator scapulae, sternocleidomastoid, middle and posterior scalenes, and anterior scalenes were measured. Disc height, anteroposterior width, and volume were measured from C2/3 to T6/7 on sagittal images. The volume of all muscles, with the exception of semispinalis capitis, increased during bed rest (P &lt; 0.025). There were no significant differences between the groups for changes in the muscles. Increased upper and midthoracic spine disc height and volume (P &lt; 0.001) was seen during bed rest, and disc height increases persisted at least 6 mo after bed rest. Increases in thoracic disc height were greater (P = 0.003) in the resistive vibration exercise group than in control. On radiological review, two subjects showed new injuries to the mid-lower thoracic spine. One of these subjects reported a midthoracic pain incident during maximal strength testing before bed rest and the other after countermeasure exercise on day 3 of bed rest. We conclude that bed rest is associated with increased disc size in the thoracic region and increases in muscle volume at the neck. The exercise device needs to be modified to ensure that load is distributed in a more physiological fashion

Heterogeneous atrophy occurs within individual lower limb muscles during 60 days of bed rest

To better understand disuse muscle atrophy, via magnetic resonance imaging, we sequentially measured muscle cross-sectional area along the entire length of all individual muscles from the hip to ankle in nine male subjects participating in 60-day head-down tilt bed rest (2nd Berlin BedRest Study; BBR2-2). We hypothesized that individual muscles would not atrophy uniformly along their length such that different regions of an individual muscle would atrophy to different extents. This hypothesis was confirmed for the adductor magnus, vasti, lateral hamstrings, medial hamstrings, rectus femoris, medial gastrocnemius, lateral gastrocnemius, tibialis posterior, flexor hallucis longus, flexor digitorum longus, peroneals, and tibialis anterior muscles (P &le; 0.004). In contrast, the hypothesis was not confirmed in the soleus, adductor brevis, gracilis, pectineus, and extensor digitorum longus muscles (P &ge; 0.20). The extent of atrophy only weakly correlated (r = -0.30, P &lt; 0.001) with the location of greatest cross-sectional area. The rate of atrophy during bed rest also differed between muscles (P &lt; 0.0001) and between some synergists. Most muscles recovered to their baseline size between 14 and 90 days after bed rest, but flexor hallucis longus, flexor digitorum longus, and lateral gastrocnemius required longer than 90 days before recovery occurred. On the basis of findings of differential atrophy between muscles and evidence in the literature, we interpret our findings of intramuscular atrophy to reflect differential disuse of functionally different muscle regions. The current work represents the first lower-limb wide survey of intramuscular differences in disuse atrophy. We conclude that intramuscular differential atrophy occurs in most, but not all, of the muscles of the lower limb during prolonged bed rest

Resistive vibration exercise reduces lower limb muscle atrophy during 56-day bed-rest.

OBJECTIVES: The current study aimed to examine the effectiveness of a resistive vibration exercise countermeasure during prolonged bed-rest in preventing lower-limb muscle atrophy. METHODS: 20 male subjects underwent 56-days of bed-rest and were assigned to either an inactive control, or a countermeasure group which performed high-load resistive exercises (including squats, heel raises and toe raises) with whole-body vibration. Magnetic resonance imaging of the lower-limbs was performed at two-weekly intervals. Volume of individual muscles was calculated. RESULTS: Countermeasure exercise reduced atrophy in the triceps surae and the vastii muscles (F>3.0, por=.071). Atrophy in the hamstring muscles was similar in both groups (F.38). The adductor longus, sartiorius and rectus femoris muscles showed little loss of muscle volume during bed-rest (F.15). CONCLUSIONS: The countermeasure exercise programme was effective in reducing atrophy in the extensors of the knee and ankle but not the hamstrings