β-Cryptoxanthin Improves p62 Accumulation and Muscle Atrophy in the Soleus Muscle of Senescence-Accelerated Mouse-Prone 1 Mice

We investigated the effects of β-cryptoxanthin on skeletal muscle atrophy in senescence-accelerated mouse-prone 1 (SAMP1) mice. For 15 weeks, SAMP1 mice were intragastrically administered vehicle or β-cryptoxanthin. At 35 weeks of age, the skeletal muscle mass in SAMP1 mice was reduced compared with that in control senescence-accelerated mouse-resistant 1 (SAMR1) mice. β-cryptoxanthin increased muscle mass with an increase in the size of muscle fibers in the soleus muscle of SAMP1 mice. The expressions of autophagy-related factors such as beclin-1, p62, LC3-I, and LC3-II were increased in the soleus muscle of SAMP1 mice; however, β-cryptoxanthin administration inhibited this increase. Unlike in SAMR1 mice, p62 was punctately distributed throughout the cytosol in the soleus muscle fibers of SAMP1 mice; however, β-cryptoxanthin inhibited this punctate distribution. The cross-sectional area of p62-positive fiber was smaller than that of p62-negative fiber, and the ratio of p62-positive fibers to p62-negative fibers was increased in SAMP1 mice. β-cryptoxanthin decreased this ratio in SAMP1 mice. Furthermore, β-cryptoxanthin decreased the autophagy-related factor expression in murine C2C12 myotube. The autophagy inhibitor bafilomycin A1, but not the proteasome inhibitor MG132, inhibited the β-cryptoxanthin-induced decrease in p62 and LC3-II expressions. These results indicate that β-cryptoxanthin inhibits the p62 accumulation in fibers and improves muscle atrophy in the soleus muscle of SAMP1 mice.

Download Full-text

Physiology of a Microgravity Environment Invited Review: Microgravity and skeletal muscle

Journal of Applied Physiology ◽

10.1152/jappl.2000.89.2.823 ◽

2000 ◽

Vol 89 (2) ◽

pp. 823-839 ◽

Cited By ~ 332

Author(s):

Robert H. Fitts ◽

Danny R. Riley ◽

Jeffrey J. Widrick

Keyword(s):

Skeletal Muscle ◽

Muscle Atrophy ◽

Thin Filament ◽

Molecular Mechanisms ◽

Skeletal Muscle Atrophy ◽

Microgravity Environment ◽

Type I ◽

Fiber Types ◽

Maximal Velocity ◽

Cross Sectional

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.

Download Full-text

Tail suspension is useful as a sarcopenia model in rats

Laboratory Animal Research ◽

10.1186/s42826-020-00083-9 ◽

2021 ◽

Vol 37 (1) ◽

Author(s):

Akira Nemoto ◽

Toru Goyagi

Keyword(s):

Skeletal Muscle ◽

Muscle Contraction ◽

Experimental Model ◽

Muscle Mass ◽

Muscle Atrophy ◽

Whole Body ◽

Skeletal Muscle Atrophy ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Simple Method

Abstract Background Sarcopenia promotes skeletal muscle atrophy and exhibits a high mortality rate. Its elucidation is of the highest clinical importance, but an animal experimental model remains controversial. In this study, we investigated a simple method for studying sarcopenia in rats. Results Muscle atrophy was investigated in 24-week-old, male, tail-suspended (TS), Sprague Dawley and spontaneously hypertensive rats (SHR). Age-matched SD rats were used as a control group. The skeletal muscle mass weight, muscle contraction, whole body tension (WBT), cross-sectional area (CSA), and Muscle RING finger-1 (MuRF-1) were assessed. Enzyme-linked immunosorbent assay was used to evaluate the MuRF-1 levels. Two muscles, the extensor digitorum longus and soleus muscles, were selected for representing fast and slow muscles, respectively. All data, except CSA, were analyzed by a one-way analysis of variance, whereas CSA was analyzed using the Kruskal-Wallis test. Muscle mass weight, muscle contraction, WBT, and CSA were significantly lower in the SHR (n = 7) and TS (n = 7) groups than in the control group, whereas MuRF-1 expression was dominant. Conclusions TS and SHR presented sarcopenic phenotypes in terms of muscle mass, muscle contraction and CSA. TS is a useful technique for providing muscle mass atrophy and weakness in an experimental model of sarcopenia in rats.

Download Full-text

Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

International Journal of Molecular Sciences ◽

10.3390/ijms21051628 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1628 ◽

Cited By ~ 3

Author(s):

Keisuke Hitachi ◽

Masashi Nakatani ◽

Shiori Funasaki ◽

Ikumi Hijikata ◽

Mizuki Maekawa ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Atrophy ◽

Skeletal Muscle Mass ◽

Muscle Size ◽

Skeletal Muscle Atrophy ◽

Myostatin Gene ◽

Expression Levels ◽

Non Coding Rnas

Skeletal muscle is a highly plastic organ that is necessary for homeostasis and health of the human body. The size of skeletal muscle changes in response to intrinsic and extrinsic stimuli. Although protein-coding RNAs including myostatin, NF-κβ, and insulin-like growth factor-1 (IGF-1), have pivotal roles in determining the skeletal muscle mass, the role of long non-coding RNAs (lncRNAs) in the regulation of skeletal muscle mass remains to be elucidated. Here, we performed expression profiling of nine skeletal muscle differentiation-related lncRNAs (DRR, DUM1, linc-MD1, linc-YY1, LncMyod, Neat1, Myoparr, Malat1, and SRA) and three genomic imprinting-related lncRNAs (Gtl2, H19, and IG-DMR) in mouse skeletal muscle. The expression levels of these lncRNAs were examined by quantitative RT-PCR in six skeletal muscle atrophy models (denervation, casting, tail suspension, dexamethasone-administration, cancer cachexia, and fasting) and two skeletal muscle hypertrophy models (mechanical overload and deficiency of the myostatin gene). Cluster analyses of these lncRNA expression levels were successfully used to categorize the muscle atrophy models into two sub-groups. In addition, the expression of Gtl2, IG-DMR, and DUM1 was altered along with changes in the skeletal muscle size. The overview of the expression levels of lncRNAs in multiple muscle atrophy and hypertrophy models provides a novel insight into the role of lncRNAs in determining the skeletal muscle mass.

Download Full-text

Two Weeks of Smoking Cessation Reverse Cigarette Smoke-Induced Skeletal Muscle Atrophy and Mitochondrial Dysfunction in Mice

Nicotine & Tobacco Research ◽

10.1093/ntr/ntaa016 ◽

2020 ◽

Cited By ~ 2

Author(s):

Tom Tanjeko Ajime ◽

Jef Serré ◽

Rob C I Wüst ◽

Guy Anselme Mpaka Messa ◽

Chiel Poffé ◽

...

Keyword(s):

Skeletal Muscle ◽

Smoking Cessation ◽

Mitochondrial Dysfunction ◽

Muscle Mass ◽

Muscle Atrophy ◽

Skeletal Muscles ◽

Skeletal Muscle Atrophy ◽

Limb Muscle ◽

Male Mice ◽

And Function

Abstract Introduction Apart from its adverse effects on the respiratory system, cigarette smoking also induces skeletal muscle atrophy and dysfunction. Whether short-term smoking cessation can restore muscle mass and function is unknown. We, therefore, studied the impact of 1- and 2-week smoking cessation on skeletal muscles in a mouse model. Methods Male mice were divided into four groups: Air-exposed (14 weeks); cigarette smoke (CS)-exposed (14 weeks); CS-exposed (13 weeks) followed by 1-week cessation; CS-exposed (12 weeks) followed by 2 weeks cessation to examine exercise capacity, physical activity levels, body composition, muscle function, capillarization, mitochondrial function and protein expression in the soleus, plantaris, and diaphragm muscles. Results CS-induced loss of body and muscle mass was significantly improved within 1 week of cessation due to increased lean and fat mass. Mitochondrial respiration and protein levels of the respiratory complexes in the soleus were lower in CS-exposed mice, but similar to control values after 2 weeks of cessation. Exposing isolated soleus muscles to CS extracts reduced mitochondrial respiration that was reversed after removing the extract. While physical activity was reduced in all groups, exercise capacity, limb muscle force, fatigue resistance, fiber size and capillarization, and diaphragm cytoplasmic HIF-1α were unaltered by CS-exposure. However, CS-induced diaphragm atrophy and increased capillary density were not seen after 2 weeks of smoking cessation. Conclusion In male mice, 2 weeks of smoking cessation reversed smoking-induced mitochondrial dysfunction, limb muscle mass loss, and diaphragm muscle atrophy, highlighting immediate benefits of cessation on skeletal muscles. Implications Our study demonstrates that CS-induced skeletal muscle mitochondrial dysfunction and atrophy are significantly improved by 2 weeks of cessation in male mice. We show for the first time that smoking cessation as short as 1 to 2 weeks is associated with immediate beneficial effects on skeletal muscle structure and function with the diaphragm being particularly sensitive to CS-exposure and cessation. This could help motivate smokers to quit smoking as early as possible. The knowledge that smoking cessation has potential positive extrapulmonary effects is particularly relevant for patients referred to rehabilitation programs and those admitted to hospitals suffering from acute or chronic muscle deterioration yet struggling with smoking cessation.

Download Full-text

Type 2 diabetes causes skeletal muscle atrophy but does not impair resistance training‐mediated myonuclear accretion and muscle mass gain in rats

Experimental Physiology ◽

10.1113/ep087585 ◽

2019 ◽

Vol 104 (10) ◽

pp. 1518-1531 ◽

Cited By ~ 1

Author(s):

Satoru Ato ◽

Kohei Kido ◽

Koji Sato ◽

Satoshi Fujita

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Resistance Training ◽

Muscle Mass ◽

Muscle Atrophy ◽

Mass Gain ◽

Skeletal Muscle Atrophy

Download Full-text

Preclinical Evaluation of a Food-Derived Functional Ingredient to Address Skeletal Muscle Atrophy

Nutrients ◽

10.3390/nu12082274 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2274

Author(s):

Roi Cal ◽

Heidi Davis ◽

Alish Kerr ◽

Audrey Wall ◽

Brendan Molloy ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Atrophy ◽

Soleus Muscle ◽

Murine Model ◽

The Body ◽

Skeletal Muscle Atrophy ◽

Type I ◽

Disuse Atrophy ◽

Tnf Α

Skeletal muscle is the metabolic powerhouse of the body, however, dysregulation of the mechanisms involved in skeletal muscle mass maintenance can have devastating effects leading to many metabolic and physiological diseases. The lack of effective solutions makes finding a validated nutritional intervention an urgent unmet medical need. In vitro testing in murine skeletal muscle cells and human macrophages was carried out to determine the effect of a hydrolysate derived from vicia faba (PeptiStrong: NPN_1) against phosphorylated S6, atrophy gene expression, and tumour necrosis factor alpha (TNF-α) secretion, respectively. Finally, the efficacy of NPN_1 on attenuating muscle waste in vivo was assessed in an atrophy murine model. Treatment of NPN_1 significantly increased the phosphorylation of S6, downregulated muscle atrophy related genes, and reduced lipopolysaccharide-induced TNF-α release in vitro. In a disuse atrophy murine model, following 18 days of NPN_1 treatment, mice exhibited a significant attenuation of muscle loss in the soleus muscle and increased the integrated expression of Type I and Type IIa fibres. At the RNA level, a significant upregulation of protein synthesis-related genes was observed in the soleus muscle following NPN_1 treatment. In vitro and preclinical results suggest that NPN_1 is an effective bioactive ingredient with great potential to prolong muscle health.

Download Full-text

MuRF1/TRIM63, Master Regulator of Muscle Mass

International Journal of Molecular Sciences ◽

10.3390/ijms21186663 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6663 ◽

Cited By ~ 1

Author(s):

Dulce Peris-Moreno ◽

Daniel Taillandier ◽

Cécile Polge

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Atrophy ◽

Molecular Mechanisms ◽

Muscle Wasting ◽

Skeletal Muscle Atrophy ◽

Cardiac Functions ◽

Important Player ◽

Cardiac Muscles ◽

Inhibitory Molecules

The E3 ubiquitin ligase MuRF1/TRIM63 was identified 20 years ago and suspected to play important roles during skeletal muscle atrophy. Since then, numerous studies have been conducted to decipher the roles, molecular mechanisms and regulation of this enzyme. This revealed that MuRF1 is an important player in the skeletal muscle atrophy process occurring during catabolic states, making MuRF1 a prime candidate for pharmacological treatments against muscle wasting. Indeed, muscle wasting is an associated event of several diseases (e.g., cancer, sepsis, diabetes, renal failure, etc.) and negatively impacts the prognosis of patients, which has stimulated the search for MuRF1 inhibitory molecules. However, studies on MuRF1 cardiac functions revealed that MuRF1 is also cardioprotective, revealing a yin and yang role of MuRF1, being detrimental in skeletal muscle and beneficial in the heart. This review discusses data obtained on MuRF1, both in skeletal and cardiac muscles, over the past 20 years, regarding the structure, the regulation, the location and the different functions identified, and the first inhibitors reported, and aim to draw the picture of what is known about MuRF1. The review also discusses important MuRF1 characteristics to consider for the design of future drugs to maintain skeletal muscle mass in patients with different pathologies.

Download Full-text

Mitochondrial-targeted antioxidants protect skeletal muscle against immobilization-induced muscle atrophy

Journal of Applied Physiology ◽

10.1152/japplphysiol.00591.2011 ◽

2011 ◽

Vol 111 (5) ◽

pp. 1459-1466 ◽

Cited By ~ 127

Author(s):

Kisuk Min ◽

Ashley J. Smuder ◽

Oh-sung Kwon ◽

Andreas N. Kavazis ◽

Hazel H. Szeto ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Muscle Atrophy ◽

Muscle Fibers ◽

Skeletal Muscle Atrophy ◽

Ros Production ◽

Oxygen Species ◽

Mitochondrial Ros ◽

Protease Activation ◽

Limb Immobilization

Prolonged periods of muscular inactivity (e.g., limb immobilization) result in skeletal muscle atrophy. Although it is established that reactive oxygen species (ROS) play a role in inactivity-induced skeletal muscle atrophy, the cellular pathway(s) responsible for inactivity-induced ROS production remain(s) unclear. To investigate this important issue, we tested the hypothesis that elevated mitochondrial ROS production contributes to immobilization-induced increases in oxidative stress, protease activation, and myofiber atrophy in skeletal muscle. Cause-and-effect was determined by administration of a novel mitochondrial-targeted antioxidant (SS-31) to prevent immobilization-induced mitochondrial ROS production in skeletal muscle fibers. Compared with ambulatory controls, 14 days of muscle immobilization resulted in significant muscle atrophy, along with increased mitochondrial ROS production, muscle oxidative damage, and protease activation. Importantly, treatment with a mitochondrial-targeted antioxidant attenuated the inactivity-induced increase in mitochondrial ROS production and prevented oxidative stress, protease activation, and myofiber atrophy. These results support the hypothesis that redox disturbances contribute to immobilization-induced skeletal muscle atrophy and that mitochondria are an important source of ROS production in muscle fibers during prolonged periods of inactivity.

Download Full-text

Muscle atrophy and hypoplasia with aging: impact of training and food restriction

Journal of Applied Physiology ◽

10.1152/jappl.1988.64.6.2428 ◽

1988 ◽

Vol 64 (6) ◽

pp. 2428-2432 ◽

Cited By ~ 47

Author(s):

C. K. Daw ◽

J. W. Starnes ◽

T. P. White

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Atrophy ◽

Food Restriction ◽

Skeletal Muscle Atrophy ◽

Free Access ◽

Sedentary Control ◽

Fiber Number ◽

Edl Muscle ◽

The Masses

The purpose of this work is to study the influence of aging, training, and food restriction on skeletal muscle mass and fiber number. Male Fischer 344 rats (n = 49) at 3 mo postpartum were assigned to three groups: 1) sedentary control (confined to cage), 2) exercise trained (18 m/min, 8 degrees grade, 20 min/day, 5 days/wk), or 3) food restricted (alternate days of free access and no access to food). At 12 and 27 mo postpartum the soleus and extensor digitorum longus (EDL) muscles were excised, weighed, and fiber number was quantified after HNO3 digestion. At 27 mo the masses of soleus and EDL muscles of sedentary control rats were 83 and 70%, respectively, of 12-mo values (138 +/- 5 and 151 +/- 4 mg). At 27 mo, soleus muscle mass of trained rats was 113% of sedentary control values, whereas EDL muscle mass was unaffected by training. At 27 mo, food restriction had no effect on the mass of both muscles compared with 27-mo sedentary control values. Fiber number was not affected by training or food restriction in both muscles. Fiber number for soleus and EDL muscles of combined groups declined with age by 5.6 and 4.2%, respectively. With aging, the small loss of muscle fibers can account at most for approximately 25% of the observed skeletal muscle atrophy.

Download Full-text