Effect of 40 Hz Magnetic Field Application in Posttraumatic Muscular Atrophy Development on Muscle Mass and Contractions in Rats.

Muscle atrophy refers to the deterioration of muscle tissue due to a long-term decrease in muscle function. In the present study, we simulated rectus femoris muscle atrophy experimentally and investigated the effect of pulsed electromagnetic field (PEMF) application on the atrophy development through muscle mass, maximal contraction force, and contraction-relaxation time. A quadriceps tendon rupture with a total tenotomy was created on the rats' hind limbs, inhibiting knee extension for 6 weeks, and this restriction of the movement led to the development of disuse atrophy, while the control group underwent no surgery. The operated and control groups were divided into subgroups according to PEMF application (1.5 mT for 45 days) or no PEMF. All groups were sacrificed after 6 weeks and had their entire rectus femoris removed. To measure the contraction force, the muscles were placed in an organ bath connected to a transducer. As a result of the atrophy, muscle mass and strength were reduced in the operated group, while no muscle mass loss was observed in the operated PEMF group. Furthermore, measurements of single, incomplete and full tetanic contraction force and contraction time (CT) did not change significantly in the operated group that received the PEMF application. The PEMF application prevented atrophy resulting from 6 weeks of immobility, according to the contraction parameters. The effects of PEMF on contraction force and CT provide a basis for further studies in which PEMF is investigated as a noninvasive therapy for disuse atrophy development. © 2022 Bioelectromagnetics Society.

Disuse muscle atrophy-improving effect of ninjin'yoeito in a mouse model.

Disuse syndrome indicates psychosomatic hypofunction caused by excess rest and motionless and muscle atrophy is termed disuse muscle atrophy. Disuse muscle atrophy-induced muscle weakness and hypoactivity further induces muscle atrophy, leading to a vicious cycle, and this is considered a factor causing secondary sarcopenia and subsequently frailty. Since frailty finally leads to a bedridden state requiring nursing, in facing a super-aging society, intervention for a risk factor of frailty, disuse muscle atrophy, is important. However, the main treatment of disuse muscle atrophy is physical therapy and there are fewer effective preventive and therapeutic drugs. The objective of this study was to search for Kampo medicine with a disuse muscle atrophy-improving effect. Ninjin'yoeito is classified as a qi-blood sohozai (dual supplement) in Chinese herbal medicine, and it has an action supplementing the spleen related to muscle. In addition, improvement of muscle mass and muscle weakness by ninjin'yoeito in a clinical study has been reported. In this study, the effect of ninjin'yoeito on disuse muscle atrophy was investigated. A disuse muscle atrophy model was prepared using male ICR mice. After surgery applying a ring for tail suspension, a 1-week recovery period was set. Ninjin'yoeito was administered by mixing it in the diet for 1 week after the recovery period, followed by tail suspension for 14 days. Ninjin'yoeito administration was continued until autopsy including the hindlimb suspension period. The mice were euthanized and autopsied immediately after completion of tail suspension, and the hindlimb muscles were collected. The food and water intakes during the hindlimb unloaded period, wet weight of the collected muscle, and muscle synthesis and muscle degradation-related factors in blood and muscle were evaluated. Ingestion of ninjin'yoeito inhibited tail suspension-induced reduction of the soleus muscle wet weight. In addition, an increase in the blood level of a muscle synthesis-related factor, IGF-1, and promotion of phosphorylation of mTOR and 4E-BP1 in the soleus muscle were observed. It was suggested that ninjin'yoeito has a disuse muscle atrophy-improving action. Promotion of the muscle synthesis pathway was considered the action mechanism of this.

Effects of Various Muscle Disuse States and Countermeasures on Muscle Molecular Signaling.

Skeletal muscle is capable of changing its structural parameters, metabolic rate and functional characteristics within a wide range when adapting to various loading regimens and states of the organism. Prolonged muscle inactivation leads to serious negative consequences that affect the quality of life and work capacity of people. This review examines various conditions that lead to decreased levels of muscle loading and activity and describes the key molecular mechanisms of muscle responses to these conditions. It also details the theoretical foundations of various methods preventing adverse muscle changes caused by decreased motor activity and describes these methods. A number of recent studies presented in this review make it possible to determine the molecular basis of the countermeasure methods used in rehabilitation and space medicine for many years, as well as to identify promising new approaches to rehabilitation and to form a holistic understanding of the mechanisms of gravity force control over the muscular system.

Protein Supplementation Enhances the Effects of Intermittent Loading on Skeletal Muscles by Activating the mTORC1 Signaling Pathway in a Rat Model of Disuse Atrophy.

Inactivity leads to skeletal muscle atrophy, whereas intermittent loading (IL) during hind limb unloading (HU) attenuates muscle atrophy. However, the combined effects of IL and protein supplementation on disuse muscle atrophy are unclear. Therefore, we investigated the effects of IL and a high-protein oral nutritional supplement (HP) during HU on skeletal muscle mass and protein synthesis/breakdown. Male F344 rats were assigned to the control (CON), 14-day HU (HU), IL during HU (HU + IL), and IL during HU followed by HP administration (2.6 g protein/kg/day; HU + IL + HP) groups. Soleus and gastrocnemius muscles were sampled 30 min after the last IL and HP supplementation. HU decreased relative soleus and gastrocnemius muscle masses. Relative muscle masses and p70 ribosomal protein S6 kinase/ribosomal protein S6 phosphorylation in soleus and gastrocnemius muscles were higher in the HU + IL group than the HU group and further higher in the HU + IL + HP group than the HU + IL group in gastrocnemius muscle. Therefore, protein administration plus IL effectively prevented skeletal muscle atrophy induced by disuse, potentially via enhanced activation of targets downstream of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway.

Nutritional Strategies to Offset Disuse-Induced Skeletal Muscle Atrophy and Anabolic Resistance in Older Adults: From Whole-Foods to Isolated Ingredients.

Preserving skeletal muscle mass and functional capacity is essential for healthy ageing. Transient periods of disuse and/or inactivity in combination with sub-optimal dietary intake have been shown to accelerate the age-related loss of muscle mass and strength, predisposing to disability and metabolic disease. Mechanisms underlying disuse and/or inactivity-related muscle deterioration in the older adults, whilst multifaceted, ultimately manifest in an imbalance between rates of muscle protein synthesis and breakdown, resulting in net muscle loss. To date, the most potent intervention to mitigate disuse-induced muscle deterioration is mechanical loading in the form of resistance exercise. However, the feasibility of older individuals performing resistance exercise during disuse and inactivity has been questioned, particularly as illness and injury may affect adherence and safety, as well as accessibility to appropriate equipment and physical therapists. Therefore, optimising nutritional intake during disuse events, through the introduction of protein-rich whole-foods, isolated proteins and nutrient compounds with purported pro-anabolic and anti-catabolic properties could offset impairments in muscle protein turnover and, ultimately, the degree of muscle atrophy and recovery upon re-ambulation. The current review therefore aims to provide an overview of nutritional countermeasures to disuse atrophy and anabolic resistance in older individuals.

Fortetropin inhibits disuse muscle atrophy in dogs after tibial plateau leveling osteotomy.

OBJECTIVE: To determine if a commercial myostatin reducer (Fortetropin®) would inhibit disuse muscle atrophy in dogs after a tibial plateau leveling osteotomy. DESIGN: A prospective randomized, double-blinded, placebo-controlled clinical trial. ANIMALS: One hundred client-owned dogs presenting for surgical correction of cranial cruciate ligament rupture by tibial plateau leveling osteotomy. PROCEDURES: Patients were randomly assigned into the Fortetropin® or placebo group and clients were instructed to add the assigned supplement to the dog's normal diet once daily for twelve weeks. Enrolled patients had ultrasound measurements of muscle thickness, tape measure measurements of thigh circumference, serum myostatin level assays, and static stance analysis evaluated at weeks 0, 8, and 12. RESULTS: From week 0 to week 8, there was no change for thigh circumference in the Fortetropin® group for the affected limb (-0.54cm, P = 0.31), but a significant decrease in thigh circumference for the placebo group (-1.21cm, P = 0.03). There was no significant change in serum myostatin levels of dogs in the Fortetropin® group at any time point (P>0.05), while there was a significant rise of serum myostatin levels of dogs in placebo group during the period of forced exercise restriction (week 0 to week 8; +2,892 pg/ml, P = 0.02). The percent of body weight supported by the affected limb increased in dogs treated with Fortetropin® (+7.0%, P<0.01) and the placebo group (+4.9%, P<0.01) at the end of the period of forced exercise restriction. The difference in weight bearing between the Fortetropin® and placebo groups was not statistically significant (P = 0.10). CONCLUSION: Dogs receiving Fortetropin® had a similar increase in stance force on the affected limb, no significant increase in serum myostatin levels, and no significant reduction in thigh circumference at the end of the period of forced exercise restriction compared to the placebo. These findings support the feeding of Fortetropin® to prevent disuse muscle atrophy in canine patients undergoing a tibial plateau leveling osteotomy.

Countering disuse atrophy in older adults with low-volume leucine supplementation.

Older adults are at increased risk of being bedridden and experiencing negative health outcomes including the loss of muscle tissue and functional capacity. We hypothesized that supplementing daily meals with a small quantity (3-4 g/meal) of leucine would partially preserve lean leg mass and function of older adults during bed rest. During a 7-day bed rest protocol, followed by 5 days of inpatient rehabilitation, healthy older men and women (67.8 ± 1.1 yr, 14 men; 6 women) were randomized to receive isoenergetic meals supplemented with leucine (LEU, 0.06 g/kg/meal; n = 10) or an alanine control (CON, 0.06 g/kg/meal; n = 10). Outcomes were assessed at baseline, following bed rest, and after rehabilitation. Body composition was measured by dual-energy X-ray absorptiometry. Functional capacity was assessed by knee extensor isokinetic and isometric dynamometry, peak aerobic capacity, and the short physical performance battery. Muscle fiber type, cross-sectional area, signaling protein expression levels, and single fiber characteristics were determined from biopsies of the vastus lateralis. Leucine supplementation reduced the loss of leg lean mass during bed rest (LEU vs. CON: -423 vs. -1035 ± 143 g; P = 0.008) but had limited impact on strength or endurance-based functional outcomes. Similarly, leucine had no effect on markers of anabolic signaling and protein degradation during bed rest or rehabilitation. In conclusion, providing older adults with supplemental leucine has minimal impact on total energy or protein consumption and has the potential to partially counter some, but not all, of the negative effects of inactivity on muscle health.NEW & NOTEWORTHY Skeletal muscle morphology and function in older adults was significantly compromised by 7 days of disuse. Leucine supplementation partially countered the loss of lean leg mass but did not preserve muscle function or positively impact changes at the muscle fiber level associated with bed rest or rehabilitation. Of note, our data support a relationship between myonuclear content and adaptations to muscle atrophy at the whole limb and single fiber level.

Low-Frequency Electrical Stimulation of Denervated Skeletal Muscle Retards Muscle and Trabecular Bone Loss in Aged Rats.

Electrical stimulation (ES)-induced muscle contraction has multiple effects; however, mechano-responsiveness of bone tissue declines with age. Here, we investigated whether daily low-frequency ES-induced muscle contraction treatment reduces muscle and bone loss and ameliorates bone fragility in early-stage disuse musculoskeletal atrophy in aged rats. Twenty-seven-month-old male rats were assigned to age-matched groups comprising the control (CON), sciatic nerve denervation (DN), or DN with direct low-frequency ES (DN+ES) groups. The structural and mechanical properties of the trabecular and cortical bone of the tibiae, and the morphological and functional properties of the tibialis anterior (TA) muscles were assessed one week after DN. ES-induced muscle contraction force mitigated denervation-induced muscle and trabecular bone loss and deterioration of the mechanical properties of the tibia mid-diaphysis, such as the stiffness, but not the maximal load, in aged rats. The TA muscle in the DN+ES group showed significant improvement in the myofiber cross-sectional area and muscle force relative to the DN group. These results suggest that low-frequency ES-induced muscle contraction treatment retards trabecular bone and muscle loss in aged rats in early-stage disuse musculoskeletal atrophy, and has beneficial effects on the functional properties of denervated skeletal muscle.

A transient protective effect of low-level laser irradiation against disuse-induced atrophy of rats.

Satellite cells, a population of skeletal muscular stem cells, are generally recognized as the main and, possibly, the sole source of postnatal muscle regeneration. Previous studies have revealed the potential of low-level laser (LLL) irradiation in promoting satellite cell proliferation, which, thereby, boosts the recovery of skeletal muscle from atrophy. The purpose of this study is to investigate the beneficial effect of LLL on disuse-induced atrophy. The optimal irradiation condition of LLL (808 nm) enhancing the proliferation of Pax7+ve cells, isolated from tibialis anterior (TA) muscle, was examined and applied on TA muscle of disuse-induced atrophy model of the rats accordingly. Healthy rats were used as the control. On one hand, transiently, LLL was able to postpone the progression of atrophy for 1 week through a reduction of apoptosis in Pax7-veMyoD+ve (myocyte) population. Simultaneously, a significant enhancement was observed in Pax7+veMyoD+ve population; however, most of the increased cells underwent apoptosis since the second week, which suggested an impaired maturation of the population. On the other hand, in normal control rats with LLL irradiation, a significant increase in Pax7+veMyoD+ve cells and a significant decrease of apoptosis were observed. As a result, a strengthened muscle contraction was observed. Our data showed the capability of LLL in postponing the progression of disuse-induced atrophy for the first time. Furthermore, the result of normal rats with LLL irradiation showed the effectiveness of LLL to strengthen muscle contraction in healthy control.

Resveratrol Improves Muscle Atrophy by Modulating Mitochondrial Quality Control in STZ-Induced Diabetic Mice.

SCOPE: In this study, we aim to determine the effects of resveratrol (RSV) on muscle atrophy in streptozocin-induced diabetic mice and to explore mitochondrial quality control (MQC) as a possible mechanism. METHODS AND RESULTS: The experimental mice were fed either a control diet or an identical diet containing 0.04% RSV for 8 weeks. Examinations were subsequently carried out, including the effects of RSV on muscle atrophy and muscle function, as well as on the signaling pathways related to protein degradation and MQC processes. The results show that RSV supplementation improves muscle atrophy and muscle function, attenuates the increase in ubiquitin and muscle RING-finger protein-1 (MuRF-1), and simultaneously attenuates LC3-II and cleaved caspase-3 in the skeletal muscle of diabetic mice. Moreover, RSV treatment of diabetic mice results in an increase in mitochondrial biogenesis and inhibition of the activation of mitophagy in skeletal muscle. RSV also protects skeletal muscle against excess mitochondrial fusion and fission in the diabetic mice. CONCLUSION: The results suggest that RSV ameliorates diabetes-induced skeletal muscle atrophy by modulating MQC.

Nitric oxide treatment attenuates muscle atrophy during hind limb suspension in mice.

Debilitating muscle-disuse atrophy in aging or obesity has huge socioeconomic impact. Since nitric oxide (NO) mediates muscle satellite cell activation and induces hypertrophy with exercise in old mice, we tested whether treatment with the NO donor, isosorbide dinitrate (ISDN), during hind limb suspension would reduce atrophy. Mice were suspended 18 days, with or without daily ISDN (66mg/kg). Muscles were examined for atrophy (weight, fiber diameter); regulatory changes in atrogin-1 (a negative regulator of muscle mass), myostatin (inhibits myogenesis), and satellite cell proliferation; and metabolic responses in myosin heavy chains (MyHCs), liver lipid, and hypothalamic gene expression. Suspension decreased muscle weight and weight relative to body weight between 25-55%, and gastrocnemius fiber diameter vs. CONTROLS: In young-adult mice, ISDN attenuated atrophy by half or more. In quadriceps, ISDN completely prevented the suspension-induced rise in atrogin-1 and drop in myostatin precursor, and attenuated the changes in MyHCs 1 and 2b observed in unloaded muscles without treatment. Fatty liver in suspended young-adult mice was also reduced by ISDN; suspended young mice had higher hypothalamic expression of the orexigenic agouti-related protein, Agrp than controls. Notably, a suspension-induced drop in muscle satellite cell proliferation by 25-58% was completely prevented (young mice) or attenuated (halved, in young-adult mice) by ISDN. NO-donor treatment has potential to attenuate atrophy and metabolic changes, and prevent regulatory changes during disuse and offset/prevent wasting in age-related sarcopenia or space travel. Increases in precursor proliferation resulting from NO treatment would also amplify benefits of physical therapy and exercise.

The influence of aging on the effectiveness of heat stress in preventing disuse muscle atrophy.

This study examined the aging effect on disuse muscle atrophy prevention using heat stress. Wistar rats aged 7 and 60 weeks were divided into three groups as follows: control, immobilized (Im), and immobilized and heat stressed (ImH). Heat stress was given by immersing the hindlimbs in hot water (42 °C) for 60 min, once in every 3 days and the gastrocnemius (GAS) and soleus (SOL) muscles were extracted after 14 days. Muscle-fiber types were classified using ATPase staining. Heat shock protein 70 (HSP70) was assessed through Western blotting. In GAS muscle of both groups and SOL muscle of 7-week-old rats, the fiber diameter of each muscle type in the ImH group significantly increased compared with that in the Im group. However, this could not be observed in the SOL muscle of the 60-week-old rats. The increased percentage of type-I fibers and variability of types I and II muscle-fiber diameter were evident in the SOL muscle of the 60-week rats. HSP70 was significantly elevated in the ImH group compared with in the Im group in both muscle types of both age groups. Thus, effectiveness of heat stress in the prevention of disuse muscle atrophy appears unsatisfactory in aging muscle fibers.

Membrane lipid rafts are disturbed in the response of rat skeletal muscle to short-term disuse.

Marked loss of skeletal muscle mass occurs under various conditions of disuse, but the molecular and cellular mechanisms leading to atrophy are not completely understood. We investigate early molecular events that might play a role in skeletal muscle remodeling during mechanical unloading (disuse). The effects of acute (6-12 h) hindlimb suspension on the soleus muscles from adult rats were examined. The integrity of plasma membrane lipid rafts was tested utilizing cholera toxin B subunit or fluorescent sterols. In addition, resting intracellular Ca2+ level was analyzed. Acute disuse disturbed the plasma membrane lipid-ordered phase throughout the sarcolemma and was more pronounced in junctional membrane regions. Ouabain (1 µM), which specifically inhibits the Na-K-ATPase α2 isozyme in rodent skeletal muscles, produced similar lipid raft changes in control muscles but was ineffective in suspended muscles, which showed an initial loss of α2 Na-K-ATPase activity. Lipid rafts were able to recover with cholesterol supplementation, suggesting that disturbance results from cholesterol loss. Repetitive nerve stimulation also restores lipid rafts, specifically in the junctional sarcolemma region. Disuse locally lowered the resting intracellular Ca2+ concentration only near the neuromuscular junction of muscle fibers. Our results provide evidence to suggest that the ordering of lipid rafts strongly depends on motor nerve input and may involve interactions with the α2 Na-K-ATPase. Lipid raft disturbance, accompanied by intracellular Ca2+ dysregulation, is among the earliest remodeling events induced by skeletal muscle disuse.

Impact of Neuromuscular Electrical Stimulation (NMES) on 90-Day Episode Costs and Post-Acute Care Utilization in Total Knee Replacement Patients with Disuse Atrophy.

INTRODUCTION: This study evaluated differences in: 1) total episode payments, 2) probability of hospital readmission, 3) probability of inpatient rehab facility (IRF) and utilization, and 4) probability of skilled nursing care facility (SNF) utilization in patients who had disuse atrophy and underwent a total knee arthroplasty (TKA) and either did, or did not, receive preoperative home-based neuromuscular electrical stimulation (NMES) therapy. MATERIALS AND METHODS: We used the Medicare limited dataset for a 5% sample of beneficiaries from 2014 and 2015 to construct episodes-of-care for TKA (DRG-470) patients with disuse atrophy who underwent a TKA during the 30 days prior to hospital admission and 90 days post-discharge. Patients were stratified into those who either did or did not receive pre- and postoperative NMES therapy. An ordinary least square (OLS) model was used to estimate the impact of NMES on total episode. Linear probability models were used to estimate the impact of NMES on SNF or IRF utilization and readmission. RESULTS: A $3,274 reduction in episode payments for patients who used preoperative NMES versus those who did not (p<0.001) was demonstrated. The probability of readmission was 12.7% lower for those who used preoperative NMES therapy versus those who did not (p=0.609). The probability of utilizing IRF and SNF was 56.7% (p=0.061) and 46.4% (p=<0.001) lower for those who used pre- and postoperative NMES versus those who did not, respectively. CONCLUSION: Significant reduction in total episode payments and SNF utilization for TKA patients with disuse atrophy who had NMES therapy was demonstrated.

l-Carnitine supplement reduces skeletal muscle atrophy induced by prolonged hindlimb suspension in rats.

l-Carnitine was recently found to downregulate the ubiquitin proteasome pathway (UPP) and increase insulin-like growth factor 1 concentrations in animal models. However, the effect of l-carnitine administration on disuse muscle atrophy induced by hindlimb suspension has not yet been studied. Thus, we hypothesized that l-carnitine may have a protective effect on muscle atrophy induced by hindlimb suspension via the Akt1/mTOR and/or UPP. Male Wistar rats were assigned to 3 groups: hindlimb suspension group, hindlimb suspension with l-carnitine administration (1250 mg·kg-1·day-1) group, and pair-fed group adjusted hindlimb suspension. l-Carnitine administration for 2 weeks of hindlimb suspension alleviated the decrease in weight and fiber size in the soleus muscle. In addition, l-carnitine suppressed atrogin-1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. The present study shows that l-carnitine has a protective effect against soleus muscle atrophy caused by hindlimb suspension and decreased E3 ligase messenger RNA expression, suggesting the possibility that l-carnitine protects against muscle atrophy, at least in part, through the inhibition of the UPP. These observations suggest that l-carnitine could serve as an effective supplement in the decrease of muscle atrophy caused by weightlessness in the fields of clinical and rehabilitative research.

Effects of high EPA and high DHA fish oils on changes in signaling associated with protein metabolism induced by hindlimb suspension in rats.

The effects of either eicosapentaenoic (EPA)- or docosahexaenoic (DHA)-rich fish oils on hindlimb suspension (HS)-induced muscle disuse atrophy were compared. Daily oral supplementations (0.3 mL/100 g b.w.) with mineral oil (MO) or high EPA or high DHA fish oils were performed in adult rats. After 2 weeks, the animals were subjected to HS for further 2 weeks. The treatments were maintained alongside HS At the end of 4 weeks, we evaluated: body weight gain, muscle mass and fat depots, composition of fatty acids, cross-sectional areas (CSA) of the soleus muscle and soleus muscle fibers, activities of cathepsin L and 26S proteasome, and content of carbonylated proteins in the soleus muscle. Signaling pathway activities associated with protein synthesis (Akt, p70S6K, S6, 4EBP1, and GSK3-beta) and protein degradation (atrogin-1/MAFbx, and MuRF1) were evaluated. HS decreased muscle mass, CSA of soleus muscle and soleus muscle fibers, and altered signaling associated with protein synthesis (decreased) and protein degradation (increased). The treatment with either fish oil decreased the ratio of omega-6/omega-3 fatty acids and changed protein synthesis-associated signaling. EPA-rich fish oil attenuated the changes induced by HS on 26S proteasome activity, CSA of soleus muscle fibers, and levels of p-Akt, total p70S6K, p-p70S6K/total p70S6K, p-4EBP1, p-GSK3-beta, p-ERK2, and total ERK 1/2 proteins. DHA-rich fish oil attenuated the changes induced by HS on p-4EBP1 and total ERK1 levels. The effects of EPA-rich fish oil on protein synthesis signaling were more pronounced. Both EPA- and DHA-rich fish oils did not impact skeletal muscle mass loss induced by non-inflammatory HS.

Natural Compounds Preventing Neurodegenerative Diseases Through Autophagic Activation.

Neurodegenerative diseases (NDDs) are a group of intractable diseases that significantly affect human health. To date, the pathogenesis of NDDs is still poorly understood and effective disease-modifying therapies for NDDs have not been established. NDDs share the common morphological characteristic of the deposition of abnormal proteins in the nervous system, including neurons. Autophagy is one of the major processes by which damaged organelles and abnormal proteins are removed from cells. Impairment of autophagy has been found to be involved in the pathogenesis of NDDs, and the regulation of autophagy may become a therapeutic strategy for NDDs. In recent years, some active compounds from plants have been found to regulate autophagy and exert neuroprotection against NDDs, including Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal and bulbar muscular atrophy, spinocerebellar ataxia 3, and amyotrophic lateral sclerosis, via activating autophagy. In this paper, we review recent advances in the use of active ingredients from plants for the regulation of autophagy and treatment of NDDs.

Skeletal muscle disuse atrophy is not attenuated by dietary protein supplementation in healthy older men.

Short successive periods of muscle disuse, due to injury or illness, can contribute significantly to the loss of muscle mass with aging (sarcopenia). It has been suggested that increasing the protein content of the diet may be an effective dietary strategy to attenuate muscle disuse atrophy. We hypothesized that protein supplementation twice daily would preserve muscle mass during a short period of limb immobilization. Twenty-three healthy older (69 ± 1 y) men were subjected to 5 d of one-legged knee immobilization by means of a full-leg cast with (PRO group; n = 11) or without (CON group; n = 12) administration of a dietary protein supplement (20.7 g of protein, 9.3 g of carbohydrate, and 3.0 g of fat) twice daily. Two d prior to and immediately after the immobilization period, single-slice computed tomography scans of the quadriceps and single-leg 1 repetition maximum strength tests were performed to assess muscle cross-sectional area (CSA) and leg muscle strength, respectively. Additionally, muscle biopsies were collected to assess muscle fiber characteristics as well as mRNA and protein expression of selected genes. Immobilization decreased quadriceps' CSAs by 1.5 ± 0.7% (P < 0.05) and 2.0 ± 0.6% (P < 0.05), and muscle strength by 8.3 ± 3.3% (P < 0.05) and 9.3 ± 1.6% (P < 0.05) in the CON and PRO groups, respectively, without differences between groups. Skeletal muscle myostatin, myogenin, and muscle RING-finger protein-1 (MuRF1) mRNA expression increased following immobilization in both groups (P < 0.05), whereas muscle atrophy F-box/atrogen-1 (MAFBx) mRNA expression increased in the PRO group only (P < 0.05). In conclusion, dietary protein supplementation (∼20 g twice daily) does not attenuate muscle loss during short-term muscle disuse in healthy older men. This trial was registered at clinicaltrials.gov as NCT01588808.

Electrical stimulation of denervated rat skeletal muscle retards trabecular bone loss in early stages of disuse musculoskeletal atrophy.

OBJECTIVES: We aimed to determine the intensity of muscle stimulation required to prevent structural failure as well as bone and skeletal muscle loss after denervation-induced disuse. METHODS: Seven-week-old rats (weight, 198-225 g) were randomly assigned to age-matched groups comprising control (CON), sciatic nerve denervation (DN) or direct electrical stimulation (ES) one day later [after denervation] with 4, 8 and 16 mA at 10 Hz for 30 min/day, six days/week, for one or three weeks. Bone architecture and mean osteoid thickness in histologically stained tibial sections and tension in tibialis anterior muscles were assessed at one and three weeks after denervation. RESULTS: Direct ES with 16 mA generated 23-30% maximal contraction force. Denervation significantly decreased trabecular bone volume fraction, thickness and number, connectivity density and increased trabecular separation in the DN group at weeks one and three. Osteoid thickness was significantly greater in the ES16 group at week one than in the DN and other ES groups. Trabecular bone volume significantly correlated with muscle weight. CONCLUSIONS: Relatively low-level muscle contraction induced by low-frequency, high-intensity electrical muscle stimulation delayed trabecular bone loss during the early stages (one week after DN) of musculoskeletal atrophy due to disuse.