Influence of aging and long-term unloading on the structure and function of human skeletal muscleThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

Understanding the quantitative and qualitative changes in skeletal muscle that control changes in function is crucial in the development of countermeasures to the loss of skeletal muscle function observed with real and simulated microgravity exposure (i.e., unloading) and with aging in humans. Qualitative changes that could influence the force and power producing properties of skeletal muscle are changes in the distribution of the 3 isoforms of the main motor protein myosin heavy chain (MHC), as well as the abundance of MHC, actin (the other main contractile protein), and the force distributing the connective tissue network. Numerous studies have examined quantitative and qualitative changes in skeletal muscle, from the whole muscle to the single myofiber from individuals undergoing real and simulated space flight for a few weeks to several months, as well as from aging men and women. When considering the relative content of the main functional and structural elements (i.e., myosin, actin, collagen), it appears that human muscle appropriately scales changes in size of 10%–40% induced over a relatively short time period (1–3 months) and over the lifespan (in humans 20 to 90+ years old). The main qualitative change with unloading and aging is a redistribution of the 3 MHC isoforms, which have vastly different contractile characteristics. It is now known that the response of skeletal muscle to unloading is muscle and gender specific. In summary, changes in muscle mass (quantity) combined with the alterations in MHC distribution (quality) are the primary determinants of changes in muscle function with unloading and aging. These parameters are the key components of muscle that should be targeted with countermeasures for conditions related to muscle loss, along with considerations for muscle- and gender-specific responses.

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CURRENT TOPICS FOR TEACHING SKELETAL MUSCLE PHYSIOLOGY

AJP Advances in Physiology Education ◽

10.1152/advan.2003.27.4.171 ◽

2003 ◽

Vol 27 (4) ◽

pp. 171-182

Author(s):

Susan V. Brooks

Keyword(s):

Skeletal Muscle ◽

Muscle Function ◽

Structure And Function ◽

Muscle Physiology ◽

American Physiological Society ◽

Skeletal Muscle Function ◽

Teaching Resources ◽

Muscle Structure ◽

The Stability ◽

And Function

Contractions of skeletal muscles provide the stability and power for all body movements. Consequently, any impairment in skeletal muscle function results in some degree of instability or immobility. Factors that influence skeletal muscle structure and function are therefore of great interest both scientifically and clinically. Injury, disease, and old age are among the factors that commonly contribute to impairment in skeletal muscle function. The goal of this article is to update current concepts of skeletal muscle physiology. Particular emphasis is placed on mechanisms of injury, repair, and adaptation in skeletal muscle as well as mechanisms underlying the declining skeletal muscle structure and function associated with aging. For additional materials please refer to the “Skeletal Muscle Physiology” presentation located on the American Physiological Society Archive of Teaching Resources Web site ( https://www.lifescitrc.org ).

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Mitochondria-Targeted Antioxidants and Skeletal Muscle Function

Antioxidants ◽

10.3390/antiox7080107 ◽

2018 ◽

Vol 7 (8) ◽

pp. 107 ◽

Cited By ~ 4

Author(s):

Sophie C. Broome ◽

Jonathan S. T. Woodhead ◽

Troy L. Merry

Keyword(s):

Skeletal Muscle ◽

Muscle Function ◽

Cell Signalling ◽

Skeletal Muscle Function ◽

Beneficial Effects ◽

Signalling Molecules ◽

Age Related ◽

And Function ◽

Very High ◽

Mitochondrial Capacity

One of the main sources of reactive oxygen species (ROS) in skeletal muscle is the mitochondria. Prolonged or very high ROS exposure causes oxidative damage, which can be deleterious to muscle function, and as such, there is growing interest in targeting antioxidants to the mitochondria in an effort to prevent or treat muscle dysfunction and damage associated with disease and injury. Paradoxically, however, ROS also act as important signalling molecules in controlling cellular homeostasis, and therefore caution must be taken when supplementing with antioxidants. It is possible that mitochondria-targeted antioxidants may limit oxidative stress without suppressing ROS from non-mitochondrial sources that might be important for cell signalling. Therefore, in this review, we summarise literature relating to the effect of mitochondria-targeted antioxidants on skeletal muscle function. Overall, mitochondria-targeted antioxidants appear to exert beneficial effects on mitochondrial capacity and function, insulin sensitivity and age-related declines in muscle function. However, it seems that this is dependent on the type of mitochondrial-trageted antioxidant employed, and its specific mechanism of action, rather than simply targeting to the mitochondria.

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Gender‐Specific Pulmonary Hypertension and Altered Skeletal Muscle Function in Lung‐Specific TNFα Overexpressing Mice

The FASEB Journal ◽

10.1096/fasebj.26.1_supplement.716.9 ◽

2012 ◽

Vol 26 (S1) ◽

Author(s):

Kechun Tang ◽

Yusu Gu ◽

Nancy Dalton ◽

Kirk Peterson ◽

Peter D. Wagner ◽

...

Keyword(s):

Skeletal Muscle ◽

Pulmonary Hypertension ◽

Muscle Function ◽

Skeletal Muscle Function ◽

Gender Specific

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SKELETAL MUSCLE FUNCTION AND GENDER: WOMEN AND MEN MIGHT BE DIFFERENT!

Medicine & Science in Sports & Exercise ◽

10.1097/00005768-199905001-00801 ◽

1999 ◽

Vol 31 (Supplement) ◽

pp. S180

Author(s):

Jane Kent-Braun ◽

Jan Lexell

Keyword(s):

Skeletal Muscle ◽

Muscle Function ◽

Skeletal Muscle Function ◽

And Gender

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Faculty Opinions recommendation of TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function after cigarette smoke exposure.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1556023.1047131 ◽

2010 ◽

Author(s):

Annemie Schols ◽

Harry Gosker

Keyword(s):

Skeletal Muscle ◽

Cigarette Smoke ◽

Muscle Function ◽

Smoke Exposure ◽

Tnf Alpha ◽

Cigarette Smoke Exposure ◽

Skeletal Muscle Function ◽

Mediated Reduction

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

Scientific Reports ◽

10.1038/s41598-021-90565-0 ◽

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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Fourteen days of smoking cessation improves muscle fatigue resistance and reverses markers of systemic inflammation

Scientific Reports ◽

10.1038/s41598-021-91510-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mohammad Z. Darabseh ◽

Thomas M. Maden-Wilkinson ◽

George Welbourne ◽

Rob C. I. Wüst ◽

Nessar Ahmed ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Smoking Cessation ◽

Muscle Fatigue ◽

Fatigue Resistance ◽

Systemic Inflammation ◽

Muscle Function ◽

Low Grade ◽

Skeletal Muscle Function ◽

Tnf Α

AbstractCigarette smoking has a negative effect on respiratory and skeletal muscle function and is a risk factor for various chronic diseases. To assess the effects of 14 days of smoking cessation on respiratory and skeletal muscle function, markers of inflammation and oxidative stress in humans. Spirometry, skeletal muscle function, circulating carboxyhaemoglobin levels, advanced glycation end products (AGEs), markers of oxidative stress and serum cytokines were measured in 38 non-smokers, and in 48 cigarette smokers at baseline and after 14 days of smoking cessation. Peak expiratory flow (p = 0.004) and forced expiratory volume in 1 s/forced vital capacity (p = 0.037) were lower in smokers compared to non-smokers but did not change significantly after smoking cessation. Smoking cessation increased skeletal muscle fatigue resistance (p < 0.001). Haemoglobin content, haematocrit, carboxyhaemoglobin, total AGEs, malondialdehyde, TNF-α, IL-2, IL-4, IL-6 and IL-10 (p < 0.05) levels were higher, and total antioxidant status (TAS), IL-12p70 and eosinophil numbers were lower (p < 0.05) in smokers. IL-4, IL-6, IL-10 and IL-12p70 had returned towards levels seen in non-smokers after 14 days smoking cessation (p < 0.05), and IL-2 and TNF-α showed a similar pattern but had not yet fully returned to levels seen in non-smokers. Haemoglobin, haematocrit, eosinophil count, AGEs, MDA and TAS did not significantly change with smoking cessation. Two weeks of smoking cessation was accompanied with an improved muscle fatigue resistance and a reduction in low-grade systemic inflammation in smokers.

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