scholarly journals Muscle weakness precedes atrophy during cancer cachexia and is associated with muscle-specific mitochondrial stress

2021 ◽  
Author(s):  
Luca J Delfinis ◽  
Catherine A Bellissimo ◽  
Shivam Gandhi ◽  
Sara N DiBenedetto ◽  
Megan E Rosa-Caldwell ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Muscle Weakness ◽  
Mitochondrial Respiration ◽  
Cancer Cachexia ◽  
Force Production ◽  
Post Inoculation ◽  
Cross Sectional ◽  
Mitochondrial Stress ◽  
Colon 26 ◽  
Mitochondrial Alterations

Muscle weakness and wasting are defining features of cancer-induced cachexia. Mitochondrial stress occurs before atrophy in certain muscles, but distinct responses between muscles and across time remains unclear. We aimed to determine the time-dependent and muscle-specific responses to Colon-26 (C26) cancer-induced cachexia in mice. At 2 weeks post-inoculation, the presence of small tumours did not alter body or muscle mass but decreased force production in the quadriceps and diaphragm. Pyruvate-supported mitochondrial respiration was lower in quadriceps while mitochondrial H2O2 emission was elevated in diaphragm. At 4 weeks, large tumours corresponded to lower body mass, muscle mass, and cross-sectional area of fibers in quadriceps and diaphragm. Force production in quadriceps was unchanged but remained lower in diaphragm vs control. Mitochondrial respiration was increased while H2O2 emission was unchanged in both muscles vs control. Mitochondrial creatine sensitivity was compromised in quadriceps. These findings indicate muscle weakness precedes atrophy in quadriceps and diaphragm but is linked to heterogeneous mitochondrial alterations. Eventual muscle-specific restorations in force and bioenergetics highlight how the effects of cancer on one muscle do not predict the response in another muscle. Exploring heterogeneous responses of muscles to cancer may reveal new mechanisms underlying distinct sensitivities, or resistance, to cancer cachexia.

scholarly journals Decreased specific force and power production of muscle fibers from myostatin-deficient mice are associated with a suppression of protein degradation

2011 ◽  
Vol 111 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Christopher L. Mendias ◽  
Erdan Kayupov ◽  
Joshua R. Bradley ◽  
Susan V. Brooks ◽  
Dennis R. Claflin
Keyword(s):  
Myosin Heavy Chain ◽  
Muscle Mass ◽  
Heavy Chain ◽  
Extensor Digitorum Longus ◽  
Isometric Force ◽  
Muscle Fibers ◽  
Force Production ◽  
Sectional Area ◽  
Cross Sectional ◽  
Maximum Isometric Force

Myostatin ( MSTN) is a member of the transforming growth factor-β superfamily of cytokines and is a negative regulator of skeletal muscle mass. Compared with MSTN+/+ mice, the extensor digitorum longus muscles of MSTN−/− mice exhibit hypertrophy, hyperplasia, and greater maximum isometric force production (Fo), but decreased specific maximum isometric force (sFo; Fo normalized by muscle cross-sectional area). The reason for the reduction in sFo was not known. Studies in myotubes indicate that inhibiting myostatin may increase muscle mass by decreasing the expression of the E3 ubiquitin ligase atrogin-1, which could impact the force-generating capacity and size of muscle fibers. To gain a greater understanding of the influence of myostatin on muscle contractility, we determined the impact of myostatin deficiency on the contractility of permeabilized muscle fibers and on the levels of atrogin-1 and ubiquitinated myosin heavy chain in whole muscle. We hypothesized that single fibers from MSTN−/− mice have a greater Fo, but no difference in sFo, and a decrease in atrogin-1 and ubiquitin-tagged myosin heavy chain levels. The results indicated that fibers from MSTN−/− mice have a greater cross-sectional area, but do not have a greater Fo and have a sFo that is significantly lower than fibers from MSTN+/+ mice. The extensor digitorum longus muscles from MSTN−/− mice also have reduced levels of atrogin-1 and ubiquitinated myosin heavy chain. These findings suggest that myostatin inhibition in otherwise healthy muscle increases the size of muscle fibers and decreases atrogin-1 levels, but does not increase the force production of individual muscle fibers.

Alteration of contractile force and mass in the senescent diaphragm with β2-agonist treatment

2002 ◽  
Vol 92 (3) ◽  
pp. 941-948 ◽  
Author(s):  
Wesley N. Smith ◽  
Amie Dirks ◽  
Takao Sugiura ◽  
Susan Muller ◽  
Phillip Scarpace ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Force Production ◽  
Type I ◽  
Cross Sectional ◽  
Tetanic Force ◽  
Fischer 344 ◽  
Old Rats ◽  
Β2 Agonist ◽  
Maximal Tetanic Force ◽  
Group 1

Aging is associated with a decrease in diaphragmatic maximal tetanic force production (Po) in senescent rats. Treatment with the β2-agonist clenbuterol (CB) has been shown to increase skeletal muscle mass and Po in weak locomotor skeletal muscles from dystrophic rodents. It is unknown whether CB can increase diaphragmatic mass and Po in senescent rats. Therefore, we tested the hypothesis that CB treatment will increase specific Po (i.e., force per cross-sectional area) and mass in the diaphragm of old rats. Young (5 mo) and old (23 mo) male Fischer 344 rats were randomly assigned to one of the following groups ( n = 10/group): 1) young CB treated; 2) young control; 3) old CB treated; and 4) old control. Animals were injected daily with either CB (2 mg/kg) or saline for 28 days. CB increased ( P < 0.05) the mass of the costal diaphragm in both young and old animals. CB treatment increased diaphragmatic-specific Po in old animals (∼15%; P < 0.05) but did not alter ( P > 0.05) diaphragmatic-specific Po in young animals. Biochemical analysis indicated that the improved maximal specific Po in the diaphragm of CB-treated old animals was not due to increased myofibrillar protein concentration. Analysis of the myosin heavy chain (MHC) content of the costal diaphragm revealed a CB-induced increase ( P < 0.05) in type IIb MHC and a decrease in type I, IIa, and IIx MHC in both young and old animals. These data support the hypothesis that CB treatment can restore the age-associated decline in both diaphragmatic-specific Po and muscle mass.

scholarly journals Eccentric contraction-induced myofiber growth in tumor-bearing mice

2016 ◽  
Vol 120 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Justin P. Hardee ◽  
Joshua E. Mangum ◽  
Song Gao ◽  
Shuichi Sato ◽  
Kimbell L. Hetzler ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
High Frequency ◽  
Tibialis Anterior ◽  
Cancer Cachexia ◽  
Eccentric Contraction ◽  
Muscle Contractions ◽  
Sectional Area ◽  
Amp Kinase ◽  
Cross Sectional

Cancer cachexia is characterized by the progressive loss of skeletal muscle mass. While mouse skeletal muscle's response to an acute bout of stimulated low-frequency concentric muscle contractions is disrupted by cachexia, gaps remain in our understanding of cachexia's effects on eccentric contraction-induced muscle growth. The purpose of this study was to determine whether repeated bouts of stimulated high-frequency eccentric muscle contractions [high-frequency electrical muscle stimulation (HFES)] could stimulate myofiber growth during cancer cachexia progression, and whether this training disrupted muscle signaling associated with wasting. Male Apc Min/+ mice initiating cachexia ( N = 9) performed seven bouts of HFES-induced eccentric contractions of the left tibialis anterior muscle over 2 wk. The right tibialis anterior served as the control, and mice were killed 48 h after the last stimulation. Age-matched C57BL/6 mice ( N = 9) served as wild-type controls. Apc Min/+ mice lost body weight, muscle mass, and type IIA, IIX, and IIB myofiber cross-sectional area. HFES increased myofiber cross-sectional area of all fiber types, regardless of cachexia. Cachexia increased muscle noncontractile tissue, which was attenuated by HFES. Cachexia decreased the percentage of high succinate dehydrogenase activity myofibers, which was increased by HFES, regardless of cachexia. While cachexia activated AMP kinase, STAT3, and ERK1/2 signaling, HFES decreased AMP kinase phosphorylation, independent of the suppression of STAT3. These results demonstrate that cachectic skeletal muscle can initiate a growth response to repeated eccentric muscle contractions, despite the presence of a systemic cachectic environment.

scholarly journals Time-Dependent Alterations in Liver and Adipose Mitochondrial Respiration During Colon-26 Cancer Cachexia

2018 ◽  
Vol 50 (5S) ◽  
pp. 212-213
Author(s):  
Gabriel S. Pena ◽  
Jessica L. Halle ◽  
Joseph P. Carzoli ◽  
Hector G. Paez ◽  
Michael C. Zourdos ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Cancer Cachexia ◽  
Time Dependent ◽  
Colon 26

scholarly journals Respiratory Muscle Weakness as a Risk Factor for Pneumonia in Older People

Gerontology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Tatsuma Okazaki ◽  
Yoshimi Suzukamo ◽  
Midori Miyatake ◽  
Riyo Komatsu ◽  
Masahiro Yaekashiwa ◽  
...  
Keyword(s):  
Risk Factor ◽  
Muscle Strength ◽  
Older People ◽  
Serum Albumin ◽  
Muscle Mass ◽  
Muscle Weakness ◽  
Fat Mass ◽  
Respiratory Muscle ◽  
Respiratory Muscle Strength ◽  
Respiratory Muscle Weakness

Introduction: The respiratory muscle strength regulates the effectiveness of coughing, which clears the airways and protects people from pneumonia. Sarcopenia is an aging-related loss of muscle mass and function, the worsening of which is associated with malnutrition. The loss of respiratory and swallowing muscle strength occurs with aging, but its effect on pneumonia is unclear. This study aimed to determine the risks of respiratory muscle weakness on the onset and relapse of pneumonia in older people in conjunction with other muscle-related factors such as malnutrition. Methods: We conducted a longitudinal study with 47 pneumonia inpatients and 35 non-pneumonia controls aged 70 years and older. We evaluated the strength of respiratory and swallowing muscles, muscle mass, and malnutrition (assessed by serum albumin levels and somatic fat) during admission and confirmed pneumonia relapse within 6 months. The maximal inspiratory and expiratory pressures determined the respiratory muscle strength. Swallowing muscle strength was evaluated by tongue pressure. Bioelectrical impedance analysis was used to evaluate the muscle and fat mass. Results: The respiratory muscle strength, body trunk muscle mass, serum albumin level, somatic fat mass, and tongue pressure were significantly lower in pneumonia patients than in controls. Risk factors for the onset of pneumonia were low inspiratory respiratory muscle strength (odds ratio [OR], 6.85; 95% confidence interval [CI], 1.56–30.11), low body trunk muscle mass divided by height2 (OR, 6.86; 95% CI, 1.49–31.65), and low serum albumin level (OR, 5.46; 95% CI, 1.51–19.79). For the relapse of pneumonia, low somatic fat mass divided by height2 was a risk factor (OR, 20.10; 95% CI, 2.10–192.42). Discussion/Conclusions: Respiratory muscle weakness, lower body trunk muscle mass, and malnutrition were risk factors for the onset of pneumonia in older people. For the relapse of pneumonia, malnutrition was a risk factor.

scholarly journals Gender-specific analysis for the association between trunk muscle mass and spinal pathologies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yusuke Hori ◽  
Masatoshi Hoshino ◽  
Kazuhide Inage ◽  
Masayuki Miyagi ◽  
Shinji Takahashi ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Bioelectrical Impedance ◽  
Vertical Axis ◽  
Impedance Analysis ◽  
Poor Quality ◽  
Trunk Muscle ◽  
Sagittal Vertical Axis ◽  
Cross Sectional ◽  
Lower Trunk ◽  
Significant Difference

AbstractWe investigated the relationship between trunk muscle mass and spinal pathologies by gender. This multicenter cross-sectional study included patients aged ≥ 30 years who visited a spinal outpatient clinic. Trunk and appendicular muscle mass were measured using bioelectrical impedance analysis. The Oswestry Disability Index (ODI), visual analog scale (VAS) score for low back pain, sagittal vertical axis (SVA), and EuroQol 5 Dimension (EQ5D) score were investigated to evaluate spinal pathology. The association between trunk muscle mass and these parameters was analyzed by gender using a non-linear regression model adjusted for patients’ demographics. We investigated the association between age and trunk muscle mass. We included 781 men and 957 women. Trunk muscle mass differed significantly between men and women, although it decreased with age after age 70 in both genders. Lower trunk muscle mass was significantly associated with ODI, SVA, and EQ5D score deterioration in both genders; its association with VAS was significant only in men. Most parameters deteriorated when trunk muscle mass was < 26 kg in men and < 19 kg in women. Lower trunk muscle mass was associated with lumbar disability, spinal imbalance, and poor quality of life in both genders, with significant difference in muscle mass.

Clinical implication of psoas muscle mass measurement for predicting death within 3 months in patients with incurable uterine cervical or corpus malignancy

2021 ◽  
Author(s):  
Hiroyuki Kurosu ◽  
Yukiharu Todo ◽  
Ryutaro Yamada ◽  
Kaoru Minowa ◽  
Tomohiko Tsuruta ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Muscle Mass ◽  
Cancer Cachexia ◽  
Mass Measurement ◽  
Characteristic Curve ◽  
Lumbar Vertebra ◽  
Psoas Muscle ◽  
Data Set ◽  
Cutoff Value ◽  
Computed Tomography Images

Abstract Objective The aim of this study was to find a clinical marker for identifying refractory cancer cachexia. Methods We analyzed computed tomography imaging data, which included the third lumbar vertebra, from 94 patients who died of uterine cervix or corpus malignancy. The time between the date of examination and date of death was the most important attribute for this study, and the computed tomography images were classified into &gt;3 months before death and ≤ 3 months before death. Psoas muscle mass index was defined as the left–right sum of the psoas muscle areas (cm2) at the level of third lumbar vertebra, divided by height squared (m2). Results A data set of 94 computed tomography images was obtained at baseline hospital visit, and a data set of 603 images was obtained at other times. One hundred (16.6%) of the 603 non-baseline images were scanned ≤3 months before death. Mean psoas muscle mass index change rates at &gt;3 months before death and ≤3 months before death were −1.3 and −20.1%, respectively (P &lt; 0.001). Receiver operating characteristic curve analysis yielded a cutoff value of −13.0%. The area under the curve reached a moderate accuracy level (0.777, 95% confidence interval 0.715–0.838). When we used the cutoff value to predict death within 3 months, sensitivity and specificity were 74.0 and 82.1%, respectively. Conclusions Measuring change in psoas muscle mass index might be useful for predicting cancer mortality within 3 months. It could become a potential tool for identifying refractory cancer cachexia.

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