Automated rodent in situ muscle contraction assay and myofiber organization analysis in sarcopenia animal models

2012 ◽  
Vol 112 (12) ◽  
pp. 2087-2098 ◽  
Author(s):  
H. Weber ◽  
A. Rauch ◽  
S. Adamski ◽  
K. Chakravarthy ◽  
A. Kulkarni ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Force Measurement ◽  
Muscle Performance ◽  
Area Measurement ◽  
Micro Ct ◽  
Cross Sectional ◽  
Muscle Aging ◽  
Age Related

Age-related sarcopenia results in frailty and decreased mobility, which are associated with increased falls and long-term disability in the elderly. Given the global increase in lifespan, sarcopenia is a growing, unmet medical need. This report aims to systematically characterize muscle aging in preclinical models, which may facilitate the development of sarcopenia therapies. Naïve rats and mice were subjected to noninvasive micro X-ray computed tomography (micro-CT) imaging, terminal in situ muscle function characterizations, and ATPase-based myofiber analysis. We developed a Definiens (Parsippany, NJ)-based algorithm to automate micro-CT image analysis, which facilitates longitudinal in vivo muscle mass analysis. We report development and characterization of translational in situ skeletal muscle performance assay systems in rat and mouse. The systems incorporate a custom-designed animal assay stage, resulting in enhanced force measurement precision, and LabVIEW (National Instruments, Austin, TX)-based algorithms to support automated data acquisition and data analysis. We used ATPase-staining techniques for myofibers to characterize fiber subtypes and distribution. Major parameters contributing to muscle performance were identified using data mining and integration, enabled by Labmatrix (BioFortis, Columbia, MD). These technologies enabled the systemic and accurate monitoring of muscle aging from a large number of animals. The data indicated that longitudinal muscle cross-sectional area measurement effectively monitors change of muscle mass and function during aging. Furthermore, the data showed that muscle performance during aging is also modulated by myofiber remodeling factors, such as changes in myofiber distribution patterns and changes in fiber shape, which affect myofiber interaction. This in vivo muscle assay platform has been applied to support identification and validation of novel targets for the treatment of sarcopenia.

scholarly journals Aerobic Exercise Improves Mitochondrial Function in Sarcopenia Mice Through Sestrin2 in an AMPKα2-Dependent Manner

2021 ◽  
Author(s):  
Sujuan Liu ◽  
Chunxia Yu ◽  
Lingjian Xie ◽  
Yanmei Niu ◽  
Li Fu
Keyword(s):  
Aerobic Exercise ◽  
Molecular Mechanism ◽  
Muscle Mass ◽  
Mitochondrial Function ◽  
High Morbidity ◽  
Dependent Manner ◽  
Cross Sectional ◽  
Age Related

Abstract Sarcopenia, the age-related loss of skeletal muscle mass and function, contributes to high morbidity and mortality in the older population. Regular exercise is necessary to avoid the initiation and progression of sarcopenia, in which the underlying molecular mechanism is still not clear. Our data revealed that the outcomes induced by sarcopenia, including muscle mass and strength loss, decreased cross-sectional area of gastrocnemius fiber, chronic inflammation, and increased dysfunctional mitochondria, were reversed by regulation exercise. Knockout or silencing of Sestrin2 (Sesn2) resulted in imbalanced mitochondrial fusion and fission, mitochondrial biogenesis, and mitophagy damage in vivo and in vitro, which was attenuated by aerobic exercise or overexpression of Sesn2. Moreover, we found that the effects of Sesn2 on mitochondrial function are dependent on AMP-activated protein kinase α2 (AMPKα2). This study indicates that aerobic exercise alleviates the negative effects resulting from sarcopenia via the Sesn2/AMPKα2 pathway and provides new insights into the molecular mechanism by which the Sesn2/AMPKα2 signaling axis mediates the beneficial impact of exercise on sarcopenia.

The Effects of Aging and Training on Skeletal Muscle

1998 ◽  
Vol 26 (4) ◽  
pp. 598-602 ◽  
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.

Intra- and inter-rater reliability in the cross-sectional area of feline lumbar epaxial musculature evaluated via abdominal CT scan

2019 ◽  
Vol 22 (8) ◽  
pp. 721-728
Author(s):  
Laura H Rayhel ◽  
Jessica M Quimby ◽  
Eric M Green ◽  
Valerie J Parker ◽  
Shasha Bai
Keyword(s):  
Ct Scan ◽  
Muscle Mass ◽  
Ct Images ◽  
Cross Sectional Area ◽  
Area Measurement ◽  
Thoracic Vertebrae ◽  
Sectional Area ◽  
Cross Sectional ◽  
Rater Reliability ◽  
Epaxial Muscle

Objectives The aim of this study was to evaluate the intra- and inter-rater reliability of epaxial muscle cross-sectional area measurement on feline CT images and to determine the relationship between normalized epaxial muscle area (EMA) and subjective muscle condition score (MCS). Methods Feline transverse CT images including the junction of the 13th thoracic vertebrae/13th rib head were retrospectively reviewed. Right and left epaxial muscle circumference and vertebral body height were measured and an average normalized EMA (ratio of epaxial area:vertebral height) was calculated for each image. Measurements were performed by three individuals blinded to the clinical data and were repeated 1 month later. Intra- and inter-rater reliability of EMA was assessed with concordance correlation coefficient (CCC), and Bland–Altman analysis was performed to assess bias and limits of agreement (LoA) between and within observers at different time points. In cats for which MCS data were available, EMA was compared between differing MCSs via the Kruskal–Wallis test, with Bonferroni-corrected Wilcoxon rank-sum post-hoc analysis. Results In total, 101 CT scans met the inclusion criteria for reliability analysis, 29 of which had muscle condition information available for analysis. Intra-rater EMA CCC ranged from 0.84 to 0.99 with minimal bias (range –0.16 to 0.08) and narrow LoA. Inter-rater EMA CCC ranged from 0.87 to 0.94, bias was larger (range –0.46 to 0.66) and LoA were wider when assessed between observers. Median EMA was significantly lower in cats with severe muscle atrophy (2.76, range 1.28–3.96) than in all other MCS groups ( P <0.0001 for all comparisons). Conclusions and relevance Measurement of EMA on CT showed strong intra-rater reliability, and median EMA measurements were significantly lower in cats with severe muscle wasting, as assessed on physical examination. Further studies correlating EMA to lean muscle mass in cats are needed to determine whether this method may be useful to quantify muscle mass in patients undergoing a CT scan.

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

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 &lt; .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.

scholarly journals Human skeletal muscle metabolic economy in vivo: effects of contraction intensity, age, and mobility impairment

2014 ◽  
Vol 307 (9) ◽  
pp. R1124-R1135 ◽  
Author(s):  
Anita D. Christie ◽  
Anne Tonson ◽  
Ryan G. Larsen ◽  
Jacob P. DeBlois ◽  
Jane A. Kent
Keyword(s):  
Functional Mobility ◽  
Older Individuals ◽  
Mobility Impairment ◽  
Cross Sectional ◽  
Age Related ◽  
Creatine Kinase Reaction ◽  
Voluntary Contractions ◽  
In Vivo Effects ◽  
Muscle Cross Sectional Area

We tested the hypothesis that older muscle has greater metabolic economy (ME) in vivo than young, in a manner dependent, in part, on contraction intensity. Twenty young (Y; 24 ± 1 yr, 10 women), 18 older healthy (O; 73 ± 2, 9 women) and 9 older individuals with mild-to-moderate mobility impairment (OI; 74 ± 1, 7 women) received stimulated twitches (2 Hz, 3 min) and performed nonfatiguing voluntary (20, 50, and 100% maximal; 12 s each) isometric dorsiflexion contractions. Torque-time integrals (TTI; Nm·s) were calculated and expressed relative to maximal fat-free muscle cross-sectional area (cm2), and torque variability during voluntary contractions was calculated as the coefficient of variation. Total ATP cost of contraction (mM) was determined from flux through the creatine kinase reaction, nonoxidative glycolysis and oxidative phosphorylation, and used to calculate ME (Nm·s·cm−2·mM ATP−1). While twitch torque relaxation was slower in O and OI compared with Y ( P ≤ 0.001), twitch TTI, ATP cost, and economy were similar across groups ( P ≥ 0.15), indicating comparable intrinsic muscle economy during electrically induced isometric contractions in vivo. During voluntary contractions, normalized TTI and total ATP cost did not differ significantly across groups ( P ≥ 0.20). However, ME was lower in OI than Y or O at 20% and 50% MVC ( P ≤ 0.02), and torque variability was greater in OI than Y or O at 20% MVC ( P ≤ 0.05). These results refute the hypothesis of greater muscle ME in old age, and provide support for lower ME in impaired older adults as a potential mechanism or consequence of age-related reductions in functional mobility.

Early effects of ageing on the mechanical performance of isolated locomotory (EDL) and respiratory (diaphragm) skeletal muscle using the work-loop technique

2014 ◽  
Vol 307 (6) ◽  
pp. R670-R684 ◽  
Author(s):  
Jason Tallis ◽  
Rob S. James ◽  
Alexander G. Little ◽  
Val M. Cox ◽  
Michael J. Duncan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Power Output ◽  
Muscle Performance ◽  
Maximal Power ◽  
Maximal Power Output ◽  
Age Related ◽  
Loop Technique ◽  
Edl Muscle ◽  
Work Loop

Previous isolated muscle studies examining the effects of ageing on contractility have used isometric protocols, which have been shown to have poor relevance to dynamic muscle performance in vivo. The present study uniquely uses the work-loop technique for a more realistic estimation of in vivo muscle function to examine changes in mammalian skeletal muscle mechanical properties with age. Measurements of maximal isometric stress, activation and relaxation time, maximal power output, and sustained power output during repetitive activation and recovery are compared in locomotory extensor digitorum longus (EDL) and core diaphragm muscle isolated from 3-, 10-, 30-, and 50-wk-old female mice to examine the early onset of ageing. A progressive age-related reduction in maximal isometric stress that was of greater magnitude than the decrease in maximal power output occurred in both muscles. Maximal force and power developed earlier in diaphragm than EDL muscle but demonstrated a greater age-related decline. The present study indicates that ability to sustain skeletal muscle power output through repetitive contraction is age- and muscle-dependent, which may help rationalize previously reported equivocal results from examination of the effect of age on muscular endurance. The age-related decline in EDL muscle performance is prevalent without a significant reduction in muscle mass, and biochemical analysis of key marker enzymes suggests that although there is some evidence of a more oxidative fiber type, this is not the primary contributor to the early age-related reduction in muscle contractility.

scholarly journals Molecular Regulation and Rejuvenation of Muscle Stem (Satellite) Cell Aging

2015 ◽  
Vol 7 (2) ◽  
pp. 73
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Satellite Cell ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Cell Function ◽  
Muscle Stem Cell ◽  
Muscle Aging ◽  
Age Related

BACKGROUND: Age-related muscle loss leads to lack of muscle strength, resulting in reduced posture and mobility and an increased risk of falls, all of which contribute to a decrease in quality of life. Skeletal muscle regeneration is a complex process, which is not yet completely understood.CONTENT: Skeletal muscle undergoes a progressive age-related loss in mass and function. Preservation of muscle mass depends in part on satellite cells, the resident stem cells of skeletal muscle. Reduced satellite cell function may contribute to the age-associated decrease in muscle mass. Recent studies have delineated that the aging process in organ stem cells is largely caused by age-specific changes in the differentiated niches, and that regenerative outcomes often depend on the age of the niche, rather than on stem cell age. It is likely that epigenetic states will be better define such key satellite cell features as prolonged quiescence and lineage fidelity. It is also likely that DNA and histone modifications will underlie many of the changes in aged satellite cells that account for age-related declines in functionality and rejuvenation through exposure to the systemic environment.SUMMARY: Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and regenerative capacity, which can lead to sarcopenia and increased mortality. Although the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Decreased muscle stem cell function in aging has long been shown to depend on altered environmental cues, whereas the contribution of intrinsic mechanisms remained less clear. Signals in the aged niche were shown to cause permanent defects in the ability of satellite cells to return to quiescence, ultimately also impairing the maintenance of self-renewing satellite cells. Therefore, only anti-aging strategies taking both factors, the stem cell niche and the stem cells per se, into consideration may ultimately be successful.KEYWORDS: satellite cell, muscle, aging, niche, regenerations

scholarly journals Bone structure determined by HR-MDCT does not correlate with micro-CT of lumbar vertebral biopsies: a prospective cross-sectional human in vivo study

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Matthias Pumberger ◽  
Ahi Sema Issever ◽  
Torsten Diekhoff ◽  
Christin Schwemmer ◽  
Susanne Berg ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Bone Structure ◽  
Bone Volume ◽  
Bone Architecture ◽  
Micro Ct ◽  
Cross Sectional ◽  
Trabecular Thickness ◽  
Increased Risk ◽  
Trabecular Separation

Abstract Background Osteoporosis is characterized by a deterioration of bone structure and quantity that leads to an increased risk of fractures. The primary diagnostic tool for the assessment of the bone quality is currently the dual-energy X-ray absorptiometry (DXA), which however only measures bone quantity. High-resolution multidetector computed tomography (HR-MDCT) offers an alternative approach to assess bone structure, but still lacks evidence for its validity in vivo. The objective of this study was to assess the validity of HR-MDCT for the evaluation of bone architecture in the lumbar spine. Methods We conducted a prospective cross-sectional study to compare the results of preoperative lumbar HR-MDCT scans with those from microcomputed tomography (μCT) analysis of transpedicular vertebral body biopsies. For this purpose, we included patients undergoing spinal surgery in our orthopedic department. Each patient underwent preoperative HR-MDCT scanning (L1-L4). Intraoperatively, transpedicular biopsies were obtained from intact vertebrae. Micro-CT analysis of these biopsies was used as a reference method to assess the actual bone architecture. HR-MDCT results were statistically analyzed regarding the correlation with results from μCT. Results Thirty-four patients with a mean age of 69.09 years (± 10.07) were included in the study. There was no significant correlation for any of the parameters (bone volume/total volume, trabecular separation, trabecular thickness) between μCT and HR-MDCT (bone volume/total volume: r = − 0.026 and p = 0.872; trabecular thickness: r = 0.074 and r = 6.42; and trabecular separation: r = − 0.18 and p = 0.254). Conclusion To our knowledge, this is the first study comparing in vivo HR-MDCT with μCT analysis of vertebral biopsies in human patients. Our findings suggest that lumbar HR-MDCT is not valid for the in vivo evaluation of bone architecture in the lumbar spine. New diagnostic tools for the evaluation of osteoporosis and preoperative orthopedic planning are urgently needed.

scholarly journals Effectiveness of Creatine Supplementation on Aging Muscle and Bone: Focus on Falls Prevention and Inflammation

2019 ◽  
Vol 8 (4) ◽  
pp. 488 ◽  
Author(s):  
Darren G. Candow ◽  
Scott C. Forbes ◽  
Philip D. Chilibeck ◽  
Stephen M. Cornish ◽  
Jose Antonio ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Healthy Aging ◽  
Creatine Supplementation ◽  
Falls Prevention ◽  
Muscle Performance ◽  
Low Grade ◽  
Age Related ◽  
Risk Of Falls ◽  
Aging Adults ◽  
Aging Muscle

Sarcopenia, defined as the age-related decrease in muscle mass, strength and physical performance, is associated with reduced bone mass and elevated low-grade inflammation. From a healthy aging perspective, interventions which overcome sarcopenia are clinically relevant. Accumulating evidence suggests that exogenous creatine supplementation has the potential to increase aging muscle mass, muscle performance, and decrease the risk of falls and possibly attenuate inflammation and loss of bone mineral. Therefore, the purpose of this review is to: (1) summarize the effects of creatine supplementation, with and without resistance training, in aging adults and discuss possible mechanisms of action, (2) examine the effects of creatine on bone biology and risk of falls, (3) evaluate the potential anti-inflammatory effects of creatine and (4) determine the safety of creatine supplementation in aging adults.

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