scholarly journals Inhibition of mTORC1 signaling in aged rats counteracts the decline in muscle mass and reverses multiple parameters of muscle signaling associated with sarcopenia

2019 ◽  
Author(s):  
Giselle A. Joseph ◽  
Sharon Wang ◽  
Weihua Zhou ◽  
Garrett Kimble ◽  
Herman Tse ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Fiber Type ◽  
Mammalian Target Of Rapamycin ◽  
Pharmacological Interventions ◽  
Cross Sectional ◽  
Multiple Parameters ◽  
Mtorc1 Signaling ◽  
Positive Modulator ◽  
Mtorc1 Pathway

AbstractThere is a lack of pharmacological interventions available for sarcopenia, a progressive age-associated loss of muscle mass, leading to a decline in mobility and quality of life. We found mTORC1 (mammalian target of rapamycin complex 1), a well-established critical positive modulator of mass, to be hyperactivated in sarcopenic muscle. Furthermore, inhibition of the mTORC1 pathway counteracted sarcopenia as determined by observing an increase in muscle mass and fiber type cross sectional area, surprising because mTORC1 signaling has been shown to be required for muscle mass gains in some settings. Additionally, several genes related to senescence were downregulated, while gene expression indicators of neuromuscular junction denervation were diminished using a low dose of a rapalog. Therefore mTORC1 inhibition may delay the progression of sarcopenia by directly and indirectly modulating multiple age-associated pathways, implicating mTORC1 as a therapeutic target to treat sarcopenia.

scholarly journals Partial Inhibition of mTORC1 in Aged Rats Counteracts the Decline in Muscle Mass and Reverses Molecular Signaling Associated with Sarcopenia

2019 ◽  
Vol 39 (19) ◽  
Author(s):  
Giselle A. Joseph ◽  
Sharon X. Wang ◽  
Cody E. Jacobs ◽  
Weihua Zhou ◽  
Garrett C. Kimble ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Fiber Type ◽  
Mammalian Target Of Rapamycin ◽  
Molecular Signaling ◽  
Cross Sectional ◽  
Partial Inhibition ◽  
Mtorc1 Signaling ◽  
Positive Modulator ◽  
Mtorc1 Pathway ◽  
Muscle Groups

ABSTRACT There is a lack of pharmacological interventions available for sarcopenia, a progressive age-associated loss of muscle mass, leading to a decline in mobility and quality of life. We found mTORC1 (mammalian target of rapamycin complex 1), a well-established positive modulator of muscle mass, to be surprisingly hyperactivated in sarcopenic muscle. Furthermore, partial inhibition of the mTORC1 pathway counteracted sarcopenia, as determined by observing an increase in muscle mass and fiber type cross-sectional area in select muscle groups, again surprising because mTORC1 signaling has been shown to be required for skeletal muscle mass gains in some models of hypertrophy. Additionally, several genes related to senescence were downregulated and gene expression indicators of neuromuscular junction denervation were diminished using a low dose of a “rapalog” (a pharmacological agent related to rapamycin). Therefore, partial mTORC1 inhibition may delay the progression of sarcopenia by directly and indirectly modulating multiple age-associated pathways, implicating mTORC1 as a therapeutic target to treat sarcopenia.

Hypertrophy and proliferation of skeletal muscle fibers from aged quail

1995 ◽  
Vol 78 (1) ◽  
pp. 293-299 ◽  
Author(s):  
J. A. Carson ◽  
M. Yamaguchi ◽  
S. E. Alway
Keyword(s):  
Muscle Mass ◽  
Fiber Type ◽  
Right Wing ◽  
Left Wing ◽  
Cross Sectional ◽  
Anterior Latissimus Dorsi ◽  
Fiber Number ◽  
Fiber Type Distribution ◽  
Distribution Shifts ◽  
The Right

The purpose of this study was to determined whether fibers in the anterior latissimus dorsi (ALD) muscle from aged Japanese quail have decreased hypertrophic or proliferative responses to 30 days of stretch overload compared with fibers from adult birds. Two groups of quail were studied, 12-wk-old quail (adult; n = 16) and 90-wk-old quail (aged; n = 16). The left wing of each bird was overloaded with a weight corresponding to 10% of the bird's body weight, and the right wing served as the intra-animal control. Quails were killed after 30 days of stretch overload. Total fiber number was quantified by counting all the fibers in a transverse section from the midbelly of the ALD muscle. ALD muscles in aged quails retained the capacity to increase their muscle mass (145%), total fiber number (49%), and fiber cross-sectional area (54%) in response to stretch overload. The ALD muscle in aged quail had a significantly lower increase in muscle mass (33%) and mass corrected for nonmuscle tissue (36%) compared with the ALD from young adult birds. Age had no effect on fiber type distribution shifts with stretch. These results suggest that although muscles in old birds have a substantial ability to adapt to enlarge, stretch-induced hypertrophy is attenuated in muscles from old quail.

scholarly journals Modulation of mTORC1 Signaling Pathway by HIV-1

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1090 ◽  
Author(s):  
Burkitkan Akbay ◽  
Anna Shmakova ◽  
Yegor Vassetzky ◽  
Svetlana Dokudovskaya
Keyword(s):  
Cellular Response ◽  
Cellular Proliferation ◽  
Mammalian Target Of Rapamycin ◽  
Host Cells ◽  
Promising Strategy ◽  
Mtorc1 Signaling ◽  
Mtorc1 Pathway ◽  
Recent Trends ◽  
Hiv 1

Mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cellular proliferation and survival which controls cellular response to different stresses, including viral infection. HIV-1 interferes with the mTORC1 pathway at every stage of infection. At the same time, the host cells rely on the mTORC1 pathway and autophagy to fight against virus replication and transmission. In this review, we will provide the most up-to-date picture of the role of the mTORC1 pathway in the HIV-1 life cycle, latency and HIV-related diseases. We will also provide an overview of recent trends in the targeting of the mTORC1 pathway as a promising strategy for HIV-1 eradication.

scholarly journals Assessment of Sarcopenia and Obesity in Patients with Myasthenia Gravis Using Dual-Energy X-ray Absorptiometry: A Cross-Sectional Study

2021 ◽  
Vol 11 (11) ◽  
pp. 1139
Author(s):  
Che-Cheng Chang ◽  
Yen-Kung Chen ◽  
Hou-Chang Chiu ◽  
Jiann-Horng Yeh
Keyword(s):  
Quality Of Life ◽  
Body Composition ◽  
Muscle Mass ◽  
Cross Sectional Study ◽  
Dual Energy ◽  
Sectional Study ◽  
Cross Sectional ◽  
X Ray ◽  
Composition Changes

Sarcopenia and obesity can negatively impact quality of life and cause chronic fragility, and are associated with neuromuscular diseases, including myasthenia gravis (MG). The long-term consequences of body composition changes in chronic MG remain unknown; we therefore evaluated changes in body composition, including sarcopenia, obesity, lean body mass, and the prevalence of sarcopenic obesity in patients. In this cross-sectional study, 35 patients with MG (mean age: 56.1 years) and 175 matched controls were enrolled. Body fat mass and skeletal muscle mass were measured using whole body dual-energy X-ray absorptiometry. Patients with MG exhibited a higher prevalence of obesity and higher android adiposity and total body fat percentage than those of controls. Although the prevalence of sarcopenia and sarcopenic obesity did not increase with age, there was a decrease in arm and android muscle mass in patients with MG compared with controls. Lower muscle mass percentages were correlated with increased age and MG severity, but not with corticosteroid use. Thus, MG is associated with increased risk for obesity and decreased muscle mass with aging, regardless of corticosteroid use. Therefore, accurate diagnosis of body composition changes in MG could facilitate the application of appropriate therapies to promote health, improve quality of life, and prevent fragility.

scholarly journals Quality of Life and Treatment Satisfaction with Pharmacological Interventions in Chinese Adults with Chronic Pain Due to Osteoarthritis

2020 ◽  
Author(s):  
Qingyun Xue ◽  
Huibin Long ◽  
Jianhao Lin ◽  
Dongping Du ◽  
Jin Zhou ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Treatment Satisfaction ◽  
Brief Pain Inventory ◽  
Cross Sectional Study ◽  
Pharmacological Interventions ◽  
Cross Sectional ◽  
Knee Oa ◽  
Related Quality ◽  
Health Related

Abstract Background: Aim of this multicenter, observational, cross-sectional study was to evaluate health-related quality of life (HRQoL) and treatment satisfaction of current medications in Chinese knee OA patients. Methods: Brief Pain Inventory (BPI), Treatment Satisfaction Questionnaire (TSQM-1.4), and HRQoL (EQ-5D-5L) were assessed in total of 601 OA of knee patients. Results: Mean score of EQ-5D-5L of patients with BPI-Severity ≥4 was significantly lower than those with BPI-Severity <4. All the scores of TSQM in 4 dimensions were lower in patients with BPI-Severity ≥4 than in those with BPI-Severity <4. Both HRQoL scores and TSQM scores showed a statistically significant decreasing trend with increasing BPI-Severity pain score.Conclusion: Chronic knee OA pain has a significant impact on patients’ HRQoL. More severe patients with OA were less satisfied with current treatments. Trial registration (Clinical Trials identifier): Not applicable

scholarly journals Redox Status and Muscle Pathology in Rheumatoid Arthritis: Insights from Various Rat Hindlimb Muscles

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
A. B. Oyenihi ◽  
T. Ollewagen ◽  
K. H. Myburgh ◽  
Y. S. L. Powrie ◽  
C. Smith
Keyword(s):  
Rheumatoid Arthritis ◽  
Muscle Mass ◽  
Fiber Type ◽  
Vastus Lateralis ◽  
Redox Status ◽  
Current Data ◽  
Muscle Pathology ◽  
Sprague Dawley ◽  
Cross Sectional ◽  
Rheumatoid Cachexia

Due to atrophy, muscle weakness is a common occurrence in rheumatoid arthritis (RA). The majority of human studies are conducted on the vastus lateralis muscle—a muscle with mixed fiber type—but little comparative data between multiple muscles in either rodent or human models are available. The current study therefore assessed both muscle ultrastructure and selected redox indicators across various muscles in a model of collagen-induced rheumatoid arthritis in female Sprague-Dawley rats. Only three muscles, the gastrocnemius, extensor digitorum longus (EDL), and soleus, had lower muscle mass (38%, 27%, and 25% loss of muscle mass, respectively; all at least P<0.01), while the vastus lateralis muscle mass was increased by 35% (P<0.01) in RA animals when compared to non-RA controls. However, all four muscles exhibited signs of deterioration indicative of rheumatoid cachexia. Cross-sectional area was similarly reduced in gastrocnemius, EDL, and soleus (60%, 58%, and 64%, respectively; all P<0.001), but vastus lateralis (22% smaller, P<0.05) was less affected, while collagen deposition was significantly increased in muscles. This pathology was associated with significant increases in tissue levels of reactive oxygen species (ROS) in all muscles except the vastus lateralis, while only the gastrocnemius had significantly increased levels of lipid peroxidation (TBARS) and antioxidant activity (FRAP). Current data illustrates the differential responses of different skeletal muscles of the hindlimb to a chronic inflammatory challenge both in terms of redox changes and resistance to cachexia.

scholarly journals Identifying the Structural Adaptations that Drive the Mechanical Load-Induced Growth of Skeletal Muscle: A Scoping Review

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1658 ◽  
Author(s):  
Kent W. Jorgenson ◽  
Stuart M. Phillips ◽  
Troy A. Hornberger
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Mechanical Loading ◽  
Skeletal Muscle Mass ◽  
Mechanical Load ◽  
Critical Role ◽  
Ultrastructural Changes ◽  
Clear Understanding ◽  
Cross Sectional

The maintenance of skeletal muscle mass plays a critical role in health and quality of life. One of the most potent regulators of skeletal muscle mass is mechanical loading, and numerous studies have led to a reasonably clear understanding of the macroscopic and microscopic changes that occur when the mechanical environment is altered. For instance, an increase in mechanical loading induces a growth response that is mediated, at least in part, by an increase in the cross-sectional area of the myofibers (i.e., myofiber hypertrophy). However, very little is known about the ultrastructural adaptations that drive this response. Even the most basic questions, such as whether mechanical load-induced myofiber hypertrophy is mediated by an increase in the size of the pre-existing myofibrils and/or an increase in the number myofibrils, have not been resolved. In this review, we thoroughly summarize what is currently known about the macroscopic, microscopic and ultrastructural changes that drive mechanical load-induced growth and highlight the critical gaps in knowledge that need to be filled.

scholarly journals Deletion of Growth Hormone Receptors in Postnatal Skeletal Muscle of Male Mice Does Not Alter Muscle Mass and Response to Pathological Injury

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3776-3783 ◽  
Author(s):  
Archana Vijayakumar ◽  
Nicholas J. Buffin ◽  
Emily J. Gallagher ◽  
Jeffrey Blank ◽  
Yingjie Wu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Muscle Mass ◽  
Hormone Receptors ◽  
Fiber Type ◽  
Receptor Signaling ◽  
Cross Sectional ◽  
Adult Mice ◽  
Type Composition ◽  
Insulin Receptor Signaling

In this study, we investigated whether loss of GH receptor (GHR) signaling in postnatal skeletal muscle alters muscle mass and regenerative ability in adult mice and whether this was dependent on IGF-1 receptor (IGF-1R) signaling. To do so, we used mouse models with skeletal muscle-specific loss of GHR signaling (mGHRKO), IGF-1R and insulin receptor signaling (MKR), or both GHR and IGF-1R/insulin receptor signaling (mGHRKO/MKR). We did not find a reduction in muscle cross-sectional area, fiber type composition, or response to pathological muscle injury in male mGHRKO and mGHRKO/MKR mice when compared with control and MKR mice, respectively. This could potentially be explained by unchanged skeletal muscle Igf-1 expression in mGHRKO and mGHRKO/MKR mice relative to control and MKR mice, respectively. Furthermore, MKR and mGHRKO/MKR mice, but not mGHRKO mice, demonstrated reduced fiber fusion after cardiotoxin injection, suggesting that IGF-1, and not GH, promotes fiber fusion in adult mice. In summary, our data suggest that GHR signaling in postnatal skeletal muscle does not play a significant role in regulating muscle mass or muscle regeneration. Additionally, in our model, muscle Igf-1 expression is not dependent on GHR signaling in postnatal skeletal muscle.

scholarly journals Nutrient patterns and the skeletal muscle mass index among Polish women: a cross-sectional study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna Danielewicz ◽  
Jakub Morze ◽  
Małgorzata Obara-Gołębiowska ◽  
Mariusz Przybyłowicz ◽  
Katarzyna E. Przybyłowicz
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Fibre Plant ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Nutrient Patterns ◽  
Skeletal Muscle Mass Index

AbstractAgeing involves significant changes in skeletal muscle mass and its functioning. This study aimed to identify the major nutrient patterns (NPs) present in a sample of adult Polish women and evaluate their associations with the skeletal muscle mass index (SMI). A cross-sectional study initially recruited 527 women, and a final analysis was carried out on 275 women aged 32–60 years. Nutrient intake was assessed using fourteen repetitions of 24-hour dietary recall. NPs were derived using principal component analysis. Associations between adherence to NPs and the SMI were evaluated using linear regression models. Three NPs were identified: ‘Animal Protein-Vitamins’, ‘Fibre-Plant Protein-Minerals’ and ‘Fats’. In the adjusted model, the upper tertile compared to the bottom tertile of the ‘Animal Protein-Vitamins’ NP was related to a higher SMI (β = 0.123 95% CI: 0.019; 0.227; P for 1-SD increase of NP score = 0.009). No associations between the SMI and the ‘Fibre-Plant Protein-Minerals’ and ‘Fats’ NPs were observed. Our results indicate that high adherence to animal product-rich patterns might be related to higher muscle mass in adult women. Research on the influence of dietary and nutrient patterns on the quality of muscle tissue may contribute to the setting of guidelines for nutritional protection of skeletal muscle with ageing and, consequently, dietary recommendations that would improve the quality of women’s lives at the later stage of life.

Abstract 300: The Role of Rheb-mTORC1 Pathway in Cardiac Developmental Growth and Pathological Hypertrophy

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Takahito Tamai ◽  
Tomokazu Murakawa ◽  
Osamu Yamaguchi ◽  
Shungo Hikoso ◽  
Issei Komuro ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Cross Sectional Area ◽  
Heart Weight ◽  
Sectional Area ◽  
Cross Sectional ◽  
Pathological Hypertrophy ◽  
Mtorc1 Signaling ◽  
Mtorc1 Pathway

Mammalian target of rapamycin (mTOR) is an evolutionary conserved Ser/Thr kinase and plays a key role in cellular growth. Multiprotein complexes called mTOR complex 1 (mTORC1) signaling is essential in cardiac hypertrophy. Many signaling pathways which can regulate mTORC1 activity have been previously reported, however, the regulation of mTORC1 is not fully elucidated. A small GTPase, Rheb (Ras homologue enriched in brain)-GTP activates mTORC1. In this study, to examine the contribution of Rheb in mTORC1 signaling in vivo hearts, we generated floxed Rheb mice to obtain cardiac-specific Rheb-deficient mice. First, to examine the role of Rheb-mTORC1 pathway in developmental cardiac hypertrophy, we generated Rheb-/- mice by crossing Rhebflox/flox mice with alpha MHC-Cre transgenic mice. Rheb-/- were born in Mendelian ratio. Echocardiographic analysis revealed that chamber dimension and contractile function of Rheb-/- were similar compared to those of control mice (Rheb+/+) 5 days after birth. However, all of them died between 8 and 10 days after birth due to cardiac dysfunction and heart failure. Rheb-/- exhibited cardiac dilatation and reduced contractility 8 days after birth. The heart weight to body weight ratio and the cross-sectional area of cardiomyocytes were significantly lower in Rheb-/- 8 days after birth. Next, to examine the role of Rheb-mTORC1 pathway in pathological hypertrophy, we generated conditional Rheb-/- mice by crossing Rhebflox/flox mice with Mer-Cre-Mer transgenic mice. Cardiac pressure overload was induced by means of transverse aortic constriction (TAC), and mice were sacrificed one week after TAC. The heart weight to tibia length ratio and the cross-sectional area of cardiomyocytes were significantly increased in both TAC-operated control and conditional Rheb-/- group compared to that of corresponding sham-operated group. Taken together, Rheb is not essential in pathological hypertrophy, but is essentilal in cardiac developmental hypertrophy in the post-neonatal period.

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