scholarly journals Impaired phagocytic function in CX3CR1+ tissue-resident skeletal muscle macrophages prevents muscle recovery after influenza A virus-induced pneumonia in aged mice

2019 ◽  
Author(s):  
Constance E. Runyan ◽  
Lynn C. Welch ◽  
Emilia Lecuona ◽  
Masahiko Shigemura ◽  
Luciano Amarelle ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Influenza A Virus ◽  
Muscle Function ◽  
Influenza A ◽  
Phagocytic Function ◽  
Muscle Recovery ◽  
Skeletal Muscle Function ◽  
Aged Mice ◽  
Young Mice

ABSTRACTSkeletal muscle dysfunction in survivors of pneumonia is a major cause of lasting morbidity that disproportionately affects older individuals. We found that skeletal muscle recovery was impaired in aged compared with young mice after influenza A virus-induced pneumonia. In young mice, recovery of muscle loss was associated with expansion of tissue-resident skeletal muscle macrophages and downregulation of MHC II expression, followed by a proliferation of muscle satellite cells. These findings were absent in aged mice and in mice deficient in Cx3cr1. Transcriptomic profiling of tissue-resident skeletal muscle macrophages from aged compared with young mice showed downregulation of pathways associated with phagocytosis and proteostasis, and persistent upregulation of inflammatory pathways. Consistently, skeletal muscle macrophages from aged mice failed to downregulate MHCII expression during recovery from influenza A virus induced pneumonia and showed impaired phagocytic function in vitro. Like aged animals, mice deficient in the phagocytic receptor Mertk showed no macrophage expansion, MHCII downregulation or satellite cell proliferation and failed to recover skeletal muscle function after influenza A pneumonia. Our data suggest that a loss of phagocytic function in a CX3CR1+ tissue-resident skeletal muscle macrophage population in aged mice precludes satellite cell proliferation and recovery of skeletal muscle function after influenza A pneumonia.

scholarly journals Impaired phagocytic function in CX3CR1 + tissue‐resident skeletal muscle macrophages prevents muscle recovery after influenza A virus‐induced pneumonia in old mice

Aging Cell ◽  
2020 ◽  
Vol 19 (9) ◽  
Author(s):  
Constance E. Runyan ◽  
Lynn C. Welch ◽  
Emilia Lecuona ◽  
Masahiko Shigemura ◽  
Luciano Amarelle ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Influenza A Virus ◽  
Influenza A ◽  
Phagocytic Function ◽  
Muscle Recovery ◽  
Old Mice

scholarly journals Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice

2021 ◽  
Author(s):  
Priya Balasubramanian ◽  
Anne E Schaar ◽  
Grace E Gustafson ◽  
Alex B Smith ◽  
Porsha R Howell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Receptor Agonist ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Fiber Type ◽  
Adiponectin Receptor ◽  
Mitochondrial Activity ◽  
Skeletal Muscle Function ◽  
Aged Mice

The loss of skeletal muscle function with age, known as sarcopenia, significantly reduces independence and quality of life and can have significant metabolic consequences. Although exercise is effective in treating sarcopenia it is not always a viable option clinically, and currently there are no pharmacological therapeutic interventions for sarcopenia. Here we show that chronic treatment with pan-adiponectin receptor agonist AdipoRon improved muscle function in male mice by a mechanism linked to skeletal muscle metabolism and tissue remodeling. In aged mice, 6 weeks of AdipoRon treatment improved skeletal muscle functional measures in vivo and ex vivo. Improvements were linked to changes in fiber type, including an enrichment of oxidative fibers, and an increase in mitochondrial activity. In young mice, 6 weeks of AdipoRon treatment improved contractile force and activated the energy sensing kinase AMPK and the mitochondrial regulator PGC-1a (peroxisome proliferator activated receptor gamma coactivator 1 alpha). In cultured cells, the AdipoRon induced stimulation of AMPK and PGC-1a was associated with increased mitochondrial membrane potential, reorganization of mitochondrial architecture, increased respiration, and increased ATP production. Furthermore, the ability of AdipoRon to stimulate AMPK and PGC1a was conserved in nonhuman primate cultured cells. These data show that AdipoRon is an effective agent for the prevention of sarcopenia in mice and indicate that its effects translate to primates, suggesting it may also be a suitable therapeutic for sarcopenia in clinical application.

scholarly journals Ang-(1–7) protects skeletal muscle function in aged mice

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ying Li ◽  
Jiao Song ◽  
Yangyang Jiang ◽  
Xue Yang ◽  
Li Cao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Muscle Function ◽  
Molecular Mechanisms ◽  
C2c12 Cells ◽  
Skeletal Muscle Function ◽  
Protective Function ◽  
Aged Mice ◽  
Age Related ◽  
The Impact

Abstract Background The angiotensin-converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang-(1–7)) axis has been shown to protect against the age-associated decline in skeletal muscle function. Here, we investigated the protective effects of ACE2 in mitigating the age-associated decline of skeletal muscle function and to identify the potential underlying molecular mechanisms. Methods We measured the expression levels of Ang-(1–7) in C57BL/6J mice of different ages and correlated these levels with measures of skeletal muscle function. We also investigated the expression of myocyte enhancer factor 2 A (MEF2A) in ACE2 knockout (ACE2KO) mice and its relationship with muscle function. We then treated aged ACE2KO mice for four weeks with Ang-(1–7) and characterized the levels of MEF2A and skeletal muscle function before and after treatment. We assessed the impact of Ang-(1–7) on the growth and differentiation of C2C12 cells in vitro and assessed changes in expression of the glucose transporter type 4 (Glut4). Results Aged mice showed reduced skeletal muscle function and levels of Ang-(1–7) expression in comparison to young and middle-aged mice. In ACE2KO mice, skeletal muscle function and MEF2A protein expression were significantly lower than in age-matched wild-type (WT) mice. After one month of Ang-(1–7) treatment, skeletal muscle function in the aged ACE2KO mice improved, while MEF2A protein expression was similar to that in the untreated group. In C2C12 cells, Ang-(1–7) was shown to promote along with the upregulated expression of Glut4. Conclusions The ACE2/ Ang-(1–7) axis has a protective function in skeletal muscle and administration of exogenous Ang-(1–7) can delay the age-related decline in the function of skeletal muscle.

scholarly journals Ang-(1-7) Protects Skeletal Muscle Function in Aged Mice

2021 ◽  
Author(s):  
Xiaoli Huang ◽  
Jiao Song ◽  
Yangyang Jiang ◽  
Xue Yang ◽  
Li Cao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Glucose Transporter ◽  
C2c12 Cells ◽  
Protective Effects ◽  
Skeletal Muscle Function ◽  
Aged Mice ◽  
Age Related ◽  
The Impact

Abstract Background: The angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang-(1-7)) axis has been shown to perform a protective task in the decline of the function of skeletal muscle correlated with the process of aging. In the present investigation, the protective effects of ACE2 in mitigating the age-associated decline of skeletal function and identified the potential underlying molecular mechanism mediating the process have been extensively evaluated.Methods: We measured the expression levels of Ang-(1-7) in C57BL/6J mice of different ages and correlated these levels with measures of skeletal muscle function. Also, we determine the expression of myocyte enhancer factor 2A (MEF2A) were detected in ACE2 knockout (ACE2KO) and correlated with muscle function. We then treated ACE2KO aged mice for 4 weeks with Ang-(1-7) and characterized the levels of MEF2A and skeletal muscle function before and after treatment. We assessed the impact of Ang-(1-7) on the growth and differentiation of C2C12 cells in vitro and assessed changes in the glucose transporter type 4 (Glut4) expression.Results: Aged mice showed reduced skeletal muscle function and levels of Ang-(1-7) expression in comparison to young and middle-aged mice. In ACE2KO mice, skeletal muscle function and MEF2A protein expression were significantly lower than in age-matched WT mice. After 1 month of the treatment of Ang-(1-7), the function of skeletal muscle related to the aged ACE2KO mice improved, however, the expression of MEF2A protein was similar to that in the untreated group. In C2C12 cells, Ang-(1-7) was shown to increased cell growth and differentiation characteristics along with the upregulated expression of Glut4.Conclusions: The axis of ACE2/ Ang-(1-7) has a protective task in skeletal muscle and the administration of exogenous Ang-(1-7) can delay the age-related decline in the functions of skeletal muscle.

scholarly journals Gait disturbances and muscle dysfunction in fibroblast growth factor 2 knockout mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. Homer-Bouthiette ◽  
L. Xiao ◽  
Marja M. Hurley
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Strength ◽  
Fibroblast Growth Factor ◽  
Muscle Function ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Skeletal Muscle Function ◽  
Age Related ◽  
Gait Disturbances

AbstractFibroblast growth factor 2 (FGF2) is important in musculoskeletal homeostasis, therefore the impact of reduction or Fgf2 knockout on skeletal muscle function and phenotype was determined. Gait analysis as well as muscle strength testing in young and old WT and Fgf2KO demonstrated age-related gait disturbances and reduction in muscle strength that were exacerbated in the KO condition. Fgf2 mRNA and protein were significantly decreased in skeletal muscle of old WT compared with young WT. Muscle fiber cross-sectional area was significantly reduced with increased fibrosis and inflammatory infiltrates in old WT and Fgf2KO vs. young WT. Inflammatory cells were further significantly increased in old Fgf2KO compared with old WT. Lipid-related genes and intramuscular fat was increased in old WT and old Fgf2KO with a further increase in fibro-adipocytes in old Fgf2KO compared with old WT. Impaired FGF signaling including Increased β-Klotho, Fgf21 mRNA, FGF21 protein, phosphorylated FGF receptors 1 and 3, was observed in old WT and old Fgf2KO. MAPK/ ERK1/2 was significantly increased in young and old Fgf2KO. We conclude that Fgf2KO, age-related decreased FGF2 in WT mice, and increased FGF21 in the setting of impaired Fgf2 expression likely contribute to impaired skeletal muscle function and sarcopenia in mice.

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