Testosterone suppression does not exacerbate disuse atrophy and impairs muscle recovery that is not rescued by high protein

2020 ◽  
Vol 129 (1) ◽  
pp. 5-16 ◽  
Author(s):  
Erik D. Hanson ◽  
Andrew C. Betik ◽  
Cara A. Timpani ◽  
John Tarle ◽  
Xinmei Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adverse Effects ◽  
Muscle Mass ◽  
Caloric Intake ◽  
Disuse Atrophy ◽  
Muscle Recovery ◽  
Testosterone Levels ◽  
Muscle Disuse ◽  
Low Testosterone ◽  
And Function

Low testosterone levels during skeletal muscle disuse did not worsen declines in muscle mass and function, although hypogonadism may attenuate recovery during subsequent reloading. Diets high in casein did not improve outcomes during immobilization or reloading. Practical strategies are needed that do not compromise caloric intake yet provide effective protein doses to augment these adverse effects.

Denervation-induced mitochondrial dysfunction and autophagy in skeletal muscle of apoptosis-deficient animals

2012 ◽  
Vol 303 (4) ◽  
pp. C447-C454 ◽  
Author(s):  
Michael F. N. O′Leary ◽  
Anna Vainshtein ◽  
Heather N. Carter ◽  
Yuan Zhang ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Mass ◽  
Contractile Activity ◽  
Double Knockout ◽  
Muscle Disuse ◽  
Subsarcolemmal Mitochondria ◽  
And Function ◽  
Species Production ◽  
Potential Signal

Skeletal muscle undergoes remarkable adaptations in response to chronic decreases in contractile activity, such as a loss of muscle mass, decreases in both mitochondrial content and function, as well as the activation of apoptosis. Although these adaptations are well known, questions remain regarding the signaling pathways that mediated these changes. Autophagy is an organelle turnover pathway that could contribute to these adaptations. The purpose of this study was to determine whether denervation-induced muscle disuse would result in the activation of autophagy gene expression in both wild-type (WT) and Bax/Bak double knockout (DKO) animals, which display an attenuated apoptotic response. Denervation caused a reduction in muscle mass for WT and DKO animals; however, there was a 40% attenuation in muscle atrophy in DKO animals. Mitochondrial state 3 respiration was significantly reduced, and reactive oxygen species production was increased by two- to threefold in both WT and DKO animals. Apoptotic markers, including cytosolic AIF and DNA fragmentation, were elevated in WT, but not in DKO animals following denervation. Autophagy proteins including LC3II, ULK1, ATG7, p62, and Beclin1 were increased similarly following denervation for both WT and DKO. Interestingly, denervation markedly increased the localization of LC3II to subsarcolemmal mitochondria, and this was more pronounced in the DKO animals. Thus denervation-induced muscle disuse activates both apoptotic and autophagic signaling pathways in muscle, and autophagic protein expression does not exhibit a compensatory increase in the presence of attenuated apoptosis. However, the absence of Bax and Bak may represent a potential signal to trigger mitophagy in muscle.

scholarly journals PGC-1α-Targeted Therapeutic Approaches to Enhance Muscle Recovery in Aging

2020 ◽  
Vol 17 (22) ◽  
pp. 8650
Author(s):  
Jonathan J. Petrocelli ◽  
Micah J. Drummond
Keyword(s):  
Skeletal Muscle ◽  
Sirtuin 1 ◽  
Future Application ◽  
Peroxisome Proliferator ◽  
Disuse Atrophy ◽  
Older Individuals ◽  
Muscle Recovery ◽  
Peroxisome Proliferator Activated Receptor ◽  
Muscle Disuse ◽  
Amp Activated Protein Kinase

Impaired muscle recovery (size and strength) following a disuse period commonly occurs in older adults. Many of these individuals are not able to adequately exercise due to pain and logistic barriers. Thus, nutritional and pharmacological therapeutics, that are translatable, are needed to promote muscle recovery following disuse in older individuals. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may be a suitable therapeutic target due to pleiotropic regulation of skeletal muscle. This review focuses on nutritional and pharmacological interventions that target PGC-1α and related Sirtuin 1 (SIRT1) and 5′ AMP-activated protein kinase (AMPKα) signaling in muscle and thus may be rapidly translated to prevent muscle disuse atrophy and promote recovery. In this review, we present several therapeutics that target PGC-1α in skeletal muscle such as leucine, β-hydroxy-β-methylbuyrate (HMB), arginine, resveratrol, metformin and combination therapies that may have future application to conditions of disuse and recovery in humans.

Maintenance of Skeletal Muscle Mitochondria in Health, Exercise, and Aging

2019 ◽  
Vol 81 (1) ◽  
pp. 19-41 ◽  
Author(s):  
David A. Hood ◽  
Jonathan M. Memme ◽  
Ashley N. Oliveira ◽  
Matthew Triolo
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Mitochondrial Function ◽  
High Functioning ◽  
Muscle Disuse ◽  
Skeletal Muscle Mitochondria ◽  
Single Bout ◽  
Atp Supply ◽  
And Function ◽  
Exercise And Aging

Mitochondria are critical organelles responsible for regulating the metabolic status of skeletal muscle. These organelles exhibit remarkable plasticity by adapting their volume, structure, and function in response to chronic exercise, disuse, aging, and disease. A single bout of exercise initiates signaling to provoke increases in mitochondrial biogenesis, balanced by the onset of organelle turnover carried out by the mitophagy pathway. This accelerated turnover ensures the presence of a high functioning network of mitochondria designed for optimal ATP supply, with the consequence of favoring lipid metabolism, maintaining muscle mass, and reducing apoptotic susceptibility over the longer term. Conversely, aging and disuse are associated with reductions in muscle mass that are in part attributable to dysregulation of the mitochondrial network and impaired mitochondrial function. Therefore, exercise represents a viable, nonpharmaceutical therapy with the potential to reverse and enhance the impaired mitochondrial function observed with aging and chronic muscle disuse.

scholarly journals Interventional strategies to combat muscle disuse atrophy in humans: focus on neuromuscular electrical stimulation and dietary protein

2018 ◽  
Vol 125 (3) ◽  
pp. 850-861 ◽  
Author(s):  
Marlou L. Dirks ◽  
Benjamin T. Wall ◽  
Luc J. C. van Loon
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Dietary Protein ◽  
Nutritional Support ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Neuromuscular Electrical Stimulation ◽  
Muscle Loss ◽  
Disuse Atrophy ◽  
Muscle Disuse

Numerous situations, such as the recovery from illness or rehabilitation after injury, necessitate a period of muscle disuse in otherwise healthy individuals. Even a few days of immobilization or bed rest can lead to substantial loss of skeletal muscle tissue and compromise metabolic health. The decline in muscle mass is attributed largely to a decline in postabsorptive and postprandial muscle protein synthesis rates. Reintroduction of some level of muscle contraction by the application of neuromuscular electrical stimulation (NMES) can augment both postabsorptive and postprandial muscle protein synthesis rates and, as such, prevent or attenuate muscle loss during short-term disuse in various clinical populations. Whereas maintenance of habitual dietary protein consumption is a prerequisite for muscle mass maintenance, supplementing dietary protein above habitual intake levels does not prevent muscle loss during disuse in otherwise healthy humans. Combining the anabolic properties of physical activity (or surrogates) with appropriate nutritional support likely further increases the capacity to preserve skeletal muscle mass during a period of disuse. Therefore, effective interventional strategies to prevent or alleviate muscle disuse atrophy should include both exercise (mimetics) and appropriate nutritional support.

scholarly journals Targeting muscle signaling pathways to minimize adverse effects of androgen deprivation

2015 ◽  
Vol 23 (1) ◽  
pp. R15-R26 ◽  
Author(s):  
Casey de Rooy ◽  
Mathis Grossmann ◽  
Jeffrey D Zajac ◽  
Ada S Cheung
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Skeletal Muscle ◽  
Adverse Effects ◽  
Muscle Mass ◽  
Muscle Growth ◽  
Androgen Deprivation ◽  
Muscle Histology ◽  
And Function ◽  
Protein Transcription

Androgen deprivation therapy (ADT) is a highly effective treatment used in ∼30% of men with prostate cancer. Adverse effects of ADT on muscle are significant with consistent losses in muscle mass. However, effects of ADT on muscle strength and physical function, of most relevance to the patient, are less well understood. This is in part due to the fact that muscle effects of ADT at the cellular, genetic and protein level, critical to the understanding of the pathophysiology of sarcopenia, have come into focus only recently. This review highlights the complexity of androgen-dependent signaling in muscle with an emphasis on recent findings in the regulation of muscle growth and muscle atrophy pathways. Furthermore, the effects of ADT and testosterone on skeletal muscle histology, gene expression and protein transcription are discussed. A better mechanistic understanding of the regulation of muscle mass and function by androgens should not only pave the way for developing targeted promyogenic interventions for men with prostate cancer receiving ADT but also may have wider implications for age-associated sarcopenia in the general population.

Estrogen status and skeletal muscle recovery from disuse atrophy

2006 ◽  
Vol 100 (6) ◽  
pp. 2012-2023 ◽  
Author(s):  
J. M. McClung ◽  
J. M. Davis ◽  
M. A. Wilson ◽  
E. C. Goldsmith ◽  
J. A. Carson
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Soleus Muscle ◽  
Female Rats ◽  
Hindlimb Suspension ◽  
Matrix Remodeling ◽  
Disuse Atrophy ◽  
Muscle Recovery ◽  
Cross Sectional ◽  
Mass Recovery

Although estrogen loss can alter skeletal muscle recovery from disuse, the specific components of muscle regrowth that are estrogen sensitive have not been described. The primary purpose of this study was to determine the components of skeletal muscle mass recovery that are biological targets of estrogen. Intact, ovariectomized (OVX), and ovariectomized with 17β-estradiol replacement (OVX+E2) female rats were subjected to hindlimb suspension for 10 days and then returned to normal cage ambulation for the duration of recovery. Soleus muscle mass returned to control levels by day 7 of recovery in the intact animals, whereas OVX soleus mass did not recover until day 14. Intact rats recovered soleus mean myofiber cross-sectional area (CSA) by day 14 of recovery, whereas the OVX soleus remained decreased (42%) at day 14. OVX mean fiber CSA did return to control levels by day 28 of recovery. The OVX+E2 treatment group recovered mean CSA at day 14, as in the intact animals. Myofibers demonstrating central nuclei were increased at day 14 in the OVX group, but not in intact or OVX+E2 animals. The percent noncontractile tissue was also increased 29% in OVX muscle at day 14, but not in either intact or OVX+E2 groups. In addition, collagen 1a mRNA was increased 45% in OVX muscle at day 14 of recovery. These results suggest that myofiber growth, myofiber regeneration, and extracellular matrix remodeling are estrogen-sensitive components of soleus muscle mass recovery from disuse atrophy.

Muscle disuse atrophy is not accompanied by changes in skeletal muscle satellite cell content

2013 ◽  
Vol 126 (8) ◽  
pp. 557-566 ◽  
Author(s):  
Tim Snijders ◽  
Benjamin T. Wall ◽  
Marlou L. Dirks ◽  
Joan M. G. Senden ◽  
Fred Hartgens ◽  
...  
Keyword(s):  
Satellite Cell ◽  
Muscle Mass ◽  
Type I ◽  
Type Ii ◽  
Disuse Atrophy ◽  
Muscle Satellite Cell ◽  
Cell Content ◽  
Muscle Disuse ◽  
Skeletal Muscle Satellite Cell ◽  
Fibre Atrophy

Two weeks of muscle disuse led to a loss in muscle mass and strength. The loss in muscle mass was attributed to both type I and type II muscle fibre atrophy, and was not accompanied by a decline in satellite cell content.

scholarly journals Skeletal muscle PGC-1β signaling is sufficient to drive an endurance exercise phenotype and to counteract components of detraining in mice

2017 ◽  
Vol 312 (5) ◽  
pp. E394-E406 ◽  
Author(s):  
Samuel Lee ◽  
Teresa C. Leone ◽  
Lisa Rogosa ◽  
John Rumsey ◽  
Julio Ayala ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Early Stage ◽  
Peroxisome Proliferator ◽  
Disuse Atrophy ◽  
Proof Of Concept ◽  
Peroxisome Proliferator Activated Receptor ◽  
Muscle Disuse ◽  
Training Response

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response. Lastly, PGC-1β overexpression during the detraining period resulted in partial prevention of the detraining response. Specifically, an increase in the plateau at which O2 uptake (V̇o2) did not change from baseline with increasing treadmill speed [peak V̇o2 (ΔV̇o2max)] was maintained in trained mice with PGC-1β overexpression in muscle 6 wk after cessation of training. However, other detraining responses, including changes in running performance and in situ half relaxation time (a measure of contractility), were not affected by PGC-1β overexpression. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training, suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in preclinical models of muscle disuse atrophy.

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