Age-related changes in isolated mouse skeletal muscle function are dependent on sex, muscle, and contractility mode

The present study aimed to simultaneously examine the age-related, muscle-specific, sex-specific, and contractile mode-specific changes in isolated mouse skeletal muscle function and morphology across multiple ages. Measurements of mammalian muscle morphology, isometric force and stress (force/cross-sectional area), absolute and normalized (power/muscle mass) work-loop power across a range of contractile velocities, fatigue resistance, and myosin heavy chain (MHC) isoform concentration were measured in 232 isolated mouse (CD-1) soleus, extensor digitorum longus (EDL), and diaphragm from male and female animals aged 3, 10, 30, 52, and 78 wk. Aging resulted in increased body mass and increased soleus and EDL muscle mass, with atrophy only present for female EDL by 78 wk despite no change in MHC isoform concentration. Absolute force and power output increased up to 52 wk and to a higher level for males. A 23–36% loss of isometric stress exceeded the 14–27% loss of power normalized to muscle mass between 10 wk and 52 wk, although the loss of normalized power between 52 and 78 wk continued without further changes in stress ( P > 0.23). Males had lower power normalized to muscle mass than females by 78 wk, with the greatest decline observed for male soleus. Aging did not cause a shift toward slower contractile characteristics, with reduced fatigue resistance observed in male EDL and female diaphragm. Our findings show that the loss of muscle quality precedes the loss of absolute performance as CD-1 mice age, with the greatest effect seen in male soleus, and in most instances without muscle atrophy or an alteration in MHC isoforms.

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The Effects of Aging and Training on Skeletal Muscle

The American Journal of Sports Medicine ◽

10.1177/03635465980260042401 ◽

1998 ◽

Vol 26 (4) ◽

pp. 598-602 ◽

Cited By ~ 130

Author(s):

Donald T. Kirkendall ◽

William E. Garrett

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Function ◽

Cellular Level ◽

Type I ◽

Loss Of Function ◽

Skeletal Muscle Function ◽

Cross Sectional ◽

Age Related ◽

General Slowing

Aging results in a gradual loss of muscle function, and there are predictable age-related alterations in skeletal muscle function. The typical adult will lose muscle mass with age; the loss varies according to sex and the level of muscle activity. At the cellular level, muscles loose both cross-sectional area and fiber numbers, with type II muscle fibers being the most affected by aging. Some denervation of fibers may occur. The combination of these factors leads to an increased percentage of type I fibers in older adults. Metabolically, the glycolytic enzymes seem to be little affected by aging, but the aerobic enzymes appear to decline with age. Aged skeletal muscle produces less force and there is a general “slowing” of the mechanical characteristics of muscle. However, neither reduced muscle demand nor the subsequent loss of function is inevitable with aging. These losses can be minimized or even reversed with training. Endurance training can improve the aerobic capacity of muscle, and resistance training can improve central nervous system recruitment of muscle and increase muscle mass. Therefore, physical activity throughout life is encouraged to prevent much of the age-related impact on skeletal muscle.

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Potential Utility of Electrical Impedance Myography in Evaluating Age-Related Skeletal Muscle Function Deficits

Frontiers in Physiology ◽

10.3389/fphys.2021.666964 ◽

2021 ◽

Vol 12 ◽

Author(s):

Brian C. Clark ◽

Seward Rutkove ◽

Elmer C. Lupton ◽

Carlos J. Padilla ◽

W. David Arnold

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Function ◽

Electrical Impedance ◽

Muscle Quality ◽

Muscle Size ◽

Current Evidence ◽

Potential Utility ◽

Skeletal Muscle Function ◽

Muscle Health

Skeletal muscle function deficits associated with advancing age are due to several physiological and morphological changes including loss of muscle size and quality (conceptualized as a reduction in the intrinsic force-generating capacity of a muscle when adjusted for muscle size). Several factors can contribute to loss of muscle quality, including denervation, excitation-contraction uncoupling, increased fibrosis, and myosteatosis (excessive levels of inter- and intramuscular adipose tissue and intramyocellular lipids). These factors also adversely affect metabolic function. There is a major unmet need for tools to rapidly and easily assess muscle mass and quality in clinical settings with minimal patient and provider burden. Herein, we discuss the potential for electrical impedance myography (EIM) as a tool to evaluate muscle mass and quality in older adults. EIM applies weak, non-detectible (e.g., 400 μA), mutifrequency (e.g., 1 kHz–1 MHz) electrical currents to a muscle (or muscle group) through two excitation electrodes, and resulting voltages are measured via two sense electrodes. Measurements are fast (~5 s/muscle), simple to perform, and unaffected by factors such as hydration that may affect other simple measures of muscle status. After nearly 2 decades of study, EIM has been shown to reflect muscle health status, including the presence of atrophy, fibrosis, and fatty infiltration, in a variety of conditions (e.g., developmental growth and maturation, conditioning/deconditioning, and obesity) and neuromuscular diseases states [e.g., amyotrophic lateral sclerosis (ALS) and muscular dystrophies]. In this article, we describe prior work and current evidence of EIM’s potential utility as a measure of muscle health in aging and geriatric medicine.

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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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NEUROMUSCULAR CHANGES WITH AGING AND SARCOPENIA

Journal of Frailty & Aging ◽

10.14283/jfa.2018.35 ◽

2018 ◽

pp. 1-3

Author(s):

B.C. Clark

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Function ◽

Skeletal Muscle Mass ◽

The Past ◽

Conceptual Definition ◽

Age Related ◽

Per Se ◽

Definition Of ◽

And Function

Sarcopenia was originally conceptualized as the age-related loss of skeletal muscle mass. Over the ensuing decades, the conceptual definition of sarcopenia has changed to represent a condition in older adults that is characterized by declining muscle mass and function, with “function” most commonly conceived as muscle weakness and/or impaired physical performance (e.g., slow gait speed). Findings over the past 15-years, however, have demonstrated that changes in grip and leg extensor strength are not primarily due to muscle atrophy per se, and that to a large extent, are reflective of declines in the integrity of the nervous system. This article briefly summarizes findings relating to the complex neuromuscular mechanisms that contribute to reductions in muscle function associated with advancing age, and the implications of these findings on the development of effective therapies.

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Reference Values for Skeletal Muscle Mass – Current Concepts and Methodological Considerations

Nutrients ◽

10.3390/nu12030755 ◽

2020 ◽

Vol 12 (3) ◽

pp. 755 ◽

Cited By ~ 6

Author(s):

Carina O. Walowski ◽

Wiebke Braun ◽

Michael J. Maisch ◽

Björn Jensen ◽

Sven Peine ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Reference Values ◽

Skeletal Muscle Mass ◽

Bioelectrical Impedance ◽

Reference Population ◽

Muscle Quality ◽

Whole Body ◽

Whole Body Imaging ◽

Cross Sectional

Assessment of a low skeletal muscle mass (SM) is important for diagnosis of ageing and disease-associated sarcopenia and is hindered by heterogeneous methods and terminologies that lead to differences in diagnostic criteria among studies and even among consensus definitions. The aim of this review was to analyze and summarize previously published cut-offs for SM applied in clinical and research settings and to facilitate comparison of results between studies. Multiple published reference values for discrepant parameters of SM were identified from 64 studies and the underlying methodological assumptions and limitations are compared including different concepts for normalization of SM for body size and fat mass (FM). Single computed tomography or magnetic resonance imaging images and appendicular lean soft tissue by dual X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA) are taken as a valid substitute of total SM because they show a high correlation with results from whole body imaging in cross-sectional and longitudinal analyses. However, the random error of these methods limits the applicability of these substitutes in the assessment of individual cases and together with the systematic error limits the accurate detection of changes in SM. Adverse effects of obesity on muscle quality and function may lead to an underestimation of sarcopenia in obesity and may justify normalization of SM for FM. In conclusion, results for SM can only be compared with reference values using the same method, BIA- or DXA-device and an appropriate reference population. Limitations of proxies for total SM as well as normalization of SM for FM are important content-related issues that need to be considered in longitudinal studies, populations with obesity or older subjects.

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Age-induced oxidative stress: how does it influence skeletal muscle quantity and quality?

Journal of Applied Physiology ◽

10.1152/japplphysiol.00321.2016 ◽

2016 ◽

Vol 121 (5) ◽

pp. 1047-1052 ◽

Cited By ~ 46

Author(s):

Cory W. Baumann ◽

Dongmin Kwak ◽

Haiming M. Liu ◽

LaDora V. Thompson

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Muscle Function ◽

Strength Loss ◽

Muscle Quality ◽

Muscle Size ◽

Nitrogen Species ◽

Skeletal Muscle Function ◽

Protein Balance ◽

Ec Coupling

With advancing age, skeletal muscle function declines as a result of strength loss. These strength deficits are largely due to reductions in muscle size (i.e., quantity) and its intrinsic force-producing capacity (i.e., quality). Age-induced reductions in skeletal muscle quantity and quality can be the consequence of several factors, including accumulation of reactive oxygen and nitrogen species (ROS/RNS), also known as oxidative stress. Therefore, the purpose of this mini-review is to highlight the published literature that has demonstrated links between aging, oxidative stress, and skeletal muscle quantity or quality. In particular, we focused on how oxidative stress has the potential to reduce muscle quantity by shifting protein balance in a deficit, and muscle quality by impairing activation at the neuromuscular junction, excitation-contraction (EC) coupling at the ryanodine receptor (RyR), and cross-bridge cycling within the myofibrillar apparatus. Of these, muscle weakness due to EC coupling failure mediated by RyR dysfunction via oxidation and/or nitrosylation appears to be the strongest candidate based on the publications reviewed. However, it is clear that age-associated oxidative stress has the ability to alter strength through several mechanisms and at various locations of the muscle fiber.

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Effectiveness of impedance parameters for muscle quality evaluation in healthy men

The Journal of Physiological Sciences ◽

10.1186/s12576-020-00780-z ◽

2020 ◽

Vol 70 (1) ◽

Author(s):

Hiroki Sato ◽

Takao Nakamura ◽

Toshimasa Kusuhara ◽

Kobara Kenichi ◽

Katsushi Kuniyasu ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Function ◽

Muscle Thickness ◽

Bioelectrical Impedance ◽

Impedance Analysis ◽

Muscle Quality ◽

Stepwise Multiple Regression ◽

Skeletal Muscle Function ◽

Healthy Men ◽

Impedance Parameters

Abstract We investigated the relationship between impedance parameters and skeletal muscle function in the lower extremities, as well as the effectiveness of impedance parameters in evaluating muscle quality. Lower extremity impedance of 19 healthy men (aged 23–31 years) measured using the direct segmental multi-frequency bioelectrical impedance analysis were arc-optimized using the Cole–Cole model, following which phase angle (PA), $${R}_{i}/{R}_{e}$$ R i / R e , and β were estimated. Skeletal muscle function was assessed by muscle thickness, muscle intensity, and isometric knee extension force (IKEF). IKEF was positively correlated with PA (r = 0.58, p < 0.01) and β (r = 0.34, p < 0.05) was negatively correlated with $${R}_{i}/{R}_{e}$$ R i / R e (r = − 0.43, p < 0.01). Stepwise multiple regression analysis results revealed that PA, β, and $${R}_{i}/{R}_{e}$$ R i / R e were correlated with IKEF independently of muscle thickness. This study suggests that arc-optimized impedance parameters are effective for evaluating muscle quality and prediction of muscle strength.

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The Relationship Between Intermuscular Fat and Physical Performance Is Moderated by Muscle Area in Older Adults

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa161 ◽

2020 ◽

Vol 76 (1) ◽

pp. 115-122

Author(s):

Samaneh Farsijani ◽

Adam J Santanasto ◽

Iva Miljkovic ◽

Robert M Boudreau ◽

Bret H Goodpaster ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Physical Performance ◽

Functional Limitations ◽

Negative Association ◽

Muscle Area ◽

Cross Sectional ◽

Age Related ◽

Intermuscular Fat ◽

The Mean

Abstract Background Age-related deposition of fat in skeletal muscle is associated with functional limitations. Skeletal muscle fat may be present in people with preserved muscle mass or accompanied by muscle wasting. However, it is not clear if the association between muscle fat deposition and physical performance is moderated by muscle mass. Objective To determine whether the association between midthigh intermuscular fat and physical performance is moderated by muscle area. Methods We performed a cross-sectional analysis of the Health, Aging, and, Body Composition (ABC) study data collected in 2002–2003 (n = 1897, women: 52.2%). Midthigh muscle cross-sectional area (by computed tomography) and physical performance measures were compared across quartiles of intermuscular fat absolute area. Moderation analysis was performed to determine the conditional effect of intermuscular fat on physical performance as a function of muscle area. Conditional effects were evaluated at three levels of muscle area (mean and ± 1 standard deviation [SD]; 213.2 ± 53.2 cm2). Results Simple slope analysis showed that the negative association between intermuscular fat area (cm2) and leg strength (N·m) was of greater magnitude (beta coefficient [b], 95% confidence interval [CI] = −0.288 [−0.427, −0.148]) in participants with greater muscle area (ie, 1 SD above the mean) compared to those with lower muscle area (ie, at mean [b = −0.12 {−0.248, 0.008}] or 1 SD below the mean [b = 0.048 {−0.122, 0.217}]). Similarly, the negative association of intermuscular fat with 400-m walk speed (m/s) and chair stand (seconds) was greater in those with higher muscle areas (p < .001) compared to those with lower muscle areas. Conclusions The association between higher intermuscular fat area and impaired physical function in aging is moderated by muscle area.

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