The myonuclear domain is not maintained in skeletal muscle during either atrophy or programmed cell death

2016 ◽  
Vol 311 (4) ◽  
pp. C607-C615 ◽  
Author(s):  
Lawrence M. Schwartz ◽  
Christine Brown ◽  
Kevin McLaughlin ◽  
Wendy Smith ◽  
Carol Bigelow
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Dna Content ◽  
Sectional Area ◽  
Cross Sectional ◽  
Myonuclear Domain ◽  
Nuclear Number

Skeletal muscle mass can increase during hypertrophy or decline dramatically in response to normal or pathological signals that trigger atrophy. Many reports have documented that the number of nuclei within these cells is also plastic. It has been proposed that a yet-to-be-defined regulatory mechanism functions to maintain a relatively stable relationship between the cytoplasmic volume and nuclear number within the cell, a phenomenon known as the “myonuclear domain” hypothesis. While it is accepted that hypertrophy is typically associated with the addition of new nuclei to the muscle fiber from stem cells such as satellite cells, the loss of myonuclei during atrophy has been controversial. The intersegmental muscles from the tobacco hawkmoth Manduca sexta are composed of giant syncytial cells that undergo sequential developmental programs of atrophy and programmed cell death at the end of metamorphosis. Since the intersegmental muscles lack satellite cells or regenerative capacity, the tissue is not “contaminated” by these nonmuscle nuclei. Consequently, we monitored muscle mass, cross-sectional area, nuclear number, and cellular DNA content during atrophy and the early phases of cell death. Despite a ∼75–80% decline in muscle mass and cross-sectional area during the period under investigation, there were no reductions in nuclear number or DNA content, and the myonuclear domain was reduced by ∼85%. These data suggest that the myonuclear domain is not an intrinsic property of skeletal muscle and that nuclei persist through atrophy and programmed cell death.

scholarly journals The Effects of Calcium-β-Hydroxy-β-Methylbutyrate on Aging-Associated Apoptotic Signaling and Muscle Mass and Function in Unloaded but Nonatrophied Extensor Digitorum Longus Muscles of Aged Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Brian T. Bennett ◽  
Junaith S. Mohamed ◽  
Stephen E. Alway
Keyword(s):  
Muscle Mass ◽  
Satellite Cells ◽  
Muscle Function ◽  
Extensor Digitorum Longus ◽  
Cross Sectional Area ◽  
Extensor Digitorum ◽  
Aged Rats ◽  
Sectional Area ◽  
Cross Sectional ◽  
Apoptotic Signaling

Beta-hydroxy-beta-methylbutyrate (HMB), a naturally occurring leucine metabolite, has been shown to attenuate plantar flexor muscle loss and increase myogenic stem cell activation during reloading after a period of significant muscle wasting by disuse in old rodents. However, it was less clear if HMB would alter dorsiflexor muscle response to unloading or reloading when there was no significant atrophy that was induced by unloading. In this study, we tested if calcium HMB (Ca-HMB) would improve muscle function and alter apoptotic signaling in the extensor digitorum longus (EDL) of aged animals that were unloaded but did not undergo atrophy. The EDL muscle was unloaded for 14 days by hindlimb suspension (HS) in aged (34-36 mo.) male Fisher 344×Brown Norway rats. The rats were removed from HS and allowed normal cage ambulation for 14 days of reloading (R). Throughout the study, the rats were gavaged daily with 170 mg of Ca-HMB or water 7 days prior to HS, then throughout 14 days of HS and 14 days of recovery after removing HS. The animals’ body weights were significantly reduced by ~18% after 14 days of HS and continued to decline by ~22% during R as compared to control conditions; however, despite unloading, EDL did not atrophy by HS, nor did it increase in mass after R. No changes were observed in EDL twitch contraction time, force production, fatigue resistance, fiber cross-sectional area, or markers of nuclear apoptosis (myonuclei + satellite cells) after HS or R. While HS and R increased the proapoptotic Bax protein abundance, BCL-2 abundance was also increased as was the frequency of TUNEL-positive myonuclei and satellite cells, yet muscle mass and fiber cross-sectional area did not change and Ca-HMB treatment had no effect reducing apoptotic signaling. These data indicate that (i) increased apoptotic signaling preceded muscle atrophy or occurred without significant EDL atrophy and (ii) that Ca-HMB treatment did not improve EDL signaling, muscle mass, or muscle function in aged rats, when HS and R did not impact mass or function.

Effects of 6 months of abiraterone acetate (AA) on muscle and adipose mass in men with metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 222-222 ◽  
Author(s):  
Samuel Craig Brondfield ◽  
Vivian K. Weinberg ◽  
Kathryn M. Koepfgen ◽  
Arturo Molina ◽  
Charles J. Ryan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Wasting ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Adipose Mass

222 Background: AA, an inhibitor of androgen biosynthesis, has been shown to prolong overall survival in patients with mCRPC who have previously been treated with chemotherapy. Androgen deprivation therapy (ADT) has been shown to result in muscle wasting in prostate cancer pts. The effects of AA on progression of muscle and fat wasting have not been characterized. We evaluated whether 6 months of AA therapy altered total skeletal muscle mass or adipose mass. Methods: 10 sequential pts who responded to AA therapy for at least 6 months and had available computed tomography (CT) scans were retrospectively selected from the phase I-II COU-AA-002 study. CT image analysis was used to quantify change from baseline in total skeletal muscle and adipose tissue after 6 months of AA treatment. Skeletal muscle and adipose tissue cross-sectional area were calculated at the L3 level using Slice-O-Matic software V4.3. Previously published regression models were used to estimate fat-free mass, fat mass and skeletal muscle mass. Paired t-tests were performed to determine the change in measurements. Results: At baseline, 7 of 10 pts were overweight or obese (body mass index [BMI] > 25 kg/m2), and none were underweight. Advanced muscle wasting (sarcopenia, previously defined as the ratio of skeletal muscle cross-sectional area at L3 level to height < 52.4 cm2/m2) was present at baseline and 6 months in 9 of 10 pts. Over 6 months of AA treatment, pts lost an average of 1.9 kg ± 1.9 kg (p = 0.13). Mean changes (kg) (±standard deviation) in total skeletal muscle mass (−0.80 ± 1.71, p = 0.18) and total non-adipose mass (−1.44 ± 3.09, p = 0.17) were not significant. A significant decrease in total adipose mass (−0.61 ± 0.84, p = 0.048) was observed. Conclusions: Sarcopenia is prevalent in pts with mCRPC. AA was not related to significantly worsening sarcopenia or overall weight loss during the first 6 months of treatment; however, this may reflect a relatively short duration of therapy and/or small sample size. A significant loss of adipose tissue was observed, which is unexpected given the known effects of ADT, which increases adipose mass. Evaluation of additional AA treated patients is ongoing.

scholarly journals Passive repetitive stretching increases skeletal muscle mass and myofiber cross-sectional area in senescence-accelerated model mouse

2021 ◽  
Author(s):  
Yumin Wang ◽  
Satoshi Ikeda ◽  
Katsunori Ikoma
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Gastrocnemius Muscle ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Passive Stretching

Abstract Mechanical stimulation has benefits for muscle mass and function. Passive stretching is widely performed in clinical rehabilitation medicine. However, the hypertrophic effects of passive repetitive stretching on senescent skeletal muscles against muscle atrophy remain unknown. We used senescence-accelerated model SAM-P8 mice. The gastrocnemius muscle was passively repetitive stretched by manual ankle dorsiflexion for 15 min, 5 days a week for 2 weeks under deep anesthesia. We examined the effects of passive stretching on muscle mass, myofiber cross-sectional area, muscle fiber type and composition, satellite cell content, mRNA expression of the signaling pathways involved in muscle protein synthesis, muscle-specific ubiquitin ligases, and myogenic regulatory factors. The gastrocnemius muscle weight of the stretched side increased compared with that of the unstretched side. In addition to the increase in muscle mass, muscle fiber cross-sectional area of the stretched side was greater than that of the unstretched side. Passive repetitive stretching significantly increased the mRNA expression level of Akt, p70S6K, 4E-BP1, Myf5, myogenin, MuRF1. Passive repetitive stretching promoted skeletal muscle mass and myofiber cross-sectional area in SAM-P8 mice. These hypertrophic observations are attributable to the stretch-activated signaling pathways involved in protein turnover. These findings are applicable to clinical muscle strengthening and sarcopenia prevention.

Effects of 6 months of abiraterone acetate (AA) on muscle and adipose mass in men with metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15137-e15137
Author(s):  
Samuel Craig Brondfield ◽  
Vivian K. Weinberg ◽  
Kathryn M. Koepfgen ◽  
Arturo Molina ◽  
Charles J. Ryan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Wasting ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Adipose Mass

e15137 Background: AA, an inhibitor of androgen biosynthesis, has been shown to prolong overall survival in patients with mCRPC who have previously been treated with chemotherapy. ADT has been shown to result in muscle wasting in prostate cancer patients. The effects of AA on progression of muscle and fat wasting have not been characterized. We evaluated whether 6 months of AA therapy altered total skeletal muscle mass or adipose mass. Methods: 10 sequential patients who responded to AA therapy for at least 6 months and had available computed tomography (CT) scans were retrospectively selected from the phase I-II COU-AA-002 study. CT image analysis was used to quantify change from baseline in total skeletal muscle and adipose tissue after 6 months of AA treatment. Skeletal muscle and adipose tissue cross-sectional area were calculated at the L3 level using Slice-O-Matic software V4.3. Previously published regression models were used to estimate fat-free mass, fat mass and skeletal muscle mass. Paired t-tests were performed to determine the change in measurements. Results: At baseline, 7 of 10 patients were overweight or obese (body mass index [BMI] > 25 kg/m2), and none were underweight. Advanced muscle wasting (sarcopenia, previously defined as the ratio of skeletal muscle cross-sectional area at L3 level to height < 52.4 cm2/m2) was present at baseline and 6 months in 9 of 10 pts. Over 6 months of AA treatment, patients lost an average of 1.9 kg ± 3.6 kg (p = 0.13). Mean changes (kg) (±standard deviation) in total skeletal muscle mass (-0.80 ± 1.71, p = 0.18) and total non-adipose mass (-1.44 ± 3.09, p = 0.17) were not significant. A significant decrease in total adipose mass (-0.61 ± 0.84, p = 0.048) was observed. Conclusions: Sarcopenia is prevalent in patients with mCRPC. AA was not related to significantly worsening sarcopenia or overall weight loss during the first 6 months of treatment; however, this may reflect a relatively short duration of therapy and/or small sample size. A significant loss of adipose tissue was observed, which is unexpected given the known effects of ADT, which increases adipose mass. Evaluation of additional AA treated patients is ongoing.

scholarly journals Transdermal Estrogen Therapy Improves Gains in Skeletal Muscle Mass After 12 Weeks of Resistance Training in Early Postmenopausal Women

2021 ◽  
Vol 11 ◽  
Author(s):  
Tine Vrist Dam ◽  
Line Barner Dalgaard ◽  
Steffen Ringgaard ◽  
Frank Ted Johansen ◽  
Mads Bisgaard Bengtsen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Resistance Training ◽  
Postmenopausal Women ◽  
Muscle Mass ◽  
Estrogen Therapy ◽  
Fat Free Mass ◽  
Sectional Area ◽  
Cross Sectional ◽  
Early Postmenopausal Women ◽  
Transdermal Estrogen

ContextWomen show an accelerated loss of muscle mass around menopause, possibly related to the decline in estrogen. Furthermore, the anabolic response to resistance exercise seems to be hampered in postmenopausal women.ObjectiveWe aimed to test the hypothesis that transdermal estrogen therapy (ET) amplifies the skeletal muscle response to resistance training in early postmenopausal women.DesignA double-blinded randomized controlled study.SettingDepartment of Public Health, Aarhus University, Denmark.ParticipantsThirty-one healthy, untrained postmenopausal women no more than 5 years past menopause.Intervention(s)Supervised resistance training with placebo (PLC, n = 16) or transdermal ET (n = 15) for 12 weeks.Main Outcome Measure(s)The primary outcome parameter was a cross-sectional area of quadriceps femoris measured by magnetic resonance imaging, and secondary parameters were fat-free mass (dual-energy X-ray absorptiometry), muscle strength, and functional tests.ResultsThe increase in muscle cross-sectional area was significantly greater in the ET group (7.9%) compared with the PLC group (3.9%) (p &lt; 0.05). Similarly, the increase in whole-body fat-free mass was greater in the ET group (5.5%) than in the PLC group (2.9%) (p &lt; 0.05). Handgrip strength increased in ET (p &lt; 0.05) but did not change in the PLC group. Muscle strength parameters, jumping height, and finger strength were all improved after the training period with no difference between groups.ConclusionThe use of transdermal ET enhanced the increase in muscle mass in response to 12 weeks of progressive resistance training in early postmenopausal women.

scholarly journals CT-Determined Sarcopenia in GLIM-Defined Malnutrition and Prediction of 6-Month Mortality in Cancer Inpatients

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2647
Author(s):  
Francisco José Sánchez-Torralvo ◽  
Ignacio Ruiz-García ◽  
Victoria Contreras-Bolívar ◽  
Inmaculada González-Almendros ◽  
María Ruiz-Vico ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Nutritional Assessment ◽  
Lumbar Vertebra ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Skeletal Muscle Index ◽  
Increased Risk ◽  
Muscle Cross Sectional Area

Our objective was to evaluate the clinical application of third lumbar vertebra (L3)-computer tomography (CT)-determined sarcopenia as a marker of muscle mass in cancer inpatients diagnosed with malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and to establish its association with 6-month mortality. Methods: This was an observational, prospective study in patients from an inpatient oncology unit. We performed a nutritional assessment according to GLIM criteria, including muscle cross-sectional area at L3 by CT and skeletal muscle index (SMI). Six-month mortality was evaluated. Results: A total of 208 patients were included. The skeletal muscle cross-sectional area at L3 was 136.2 ± 32.5 cm2 in men and 98.1 ± 21.2 cm2 in women. The SMI was 47.4 ± 12.3 cm2/m2 in men and 38.7 ± 8.3 cm2/m2 in women. Sarcopenia (low SMI) was detected in 59.6% of the subjects. Using SMI as a marker of low muscle mass in application of GLIM criteria, we found 183 (87.9%) malnourished patients. There were 104 deaths (50%) at 6 months. The deceased patients had a lower skeletal muscle cross-sectional area (112.9 ± 27.9 vs. 126.1 ± 37.8 cm2; p = 0.003) and a lower SMI (41.3 ± 9.5 vs. 45.7 ± 12.9 cm2/m2; p = 0.006). An increased risk of 6-month mortality was found in malnourished patients according to GLIM criteria using SMI (HR 2.47; 95% confidence interval 1.07–5.68; p = 0.033). Conclusions: Low muscle mass, assessed by L3-CT, was observed to affect more than half of cancer inpatients. The deceased patients at 6 months had a lower skeletal muscle cross-sectional area and SMI. Malnutrition according to GLIM criteria using CT-determined sarcopenia was shown to adequately predict 6-month mortality.

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.

Lysine inhibits apoptosis in satellite cells to govern skeletal muscle growth via the JAK2-STAT3 pathway

2020 ◽  
Vol 11 (5) ◽  
pp. 3941-3951 ◽  
Author(s):  
Zhi-wen Song ◽  
Cheng-long Jin ◽  
Mao Ye ◽  
Chun-qi Gao ◽  
Hui-chao Yan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Satellite Cells ◽  
Muscle Growth ◽  
External Stress ◽  
Stat3 Pathway ◽  
Skeletal Muscle Growth

Apoptosis is programmed cell death that can be stimulated by external stress or nutrition restrictions.

scholarly journals Depletion of Pre-Transplant Skeletal Muscle Is a Significant Poor Prognostic Factor in Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3322-3322
Author(s):  
Yasuhiko Shibasaki ◽  
Kenta Kobayashi ◽  
Tatsuya Suwabe ◽  
Kyoko Fuse ◽  
Miwako Narita ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Prognostic Factor ◽  
Muscle Mass ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Hematological Disease ◽  
Cross Sectional ◽  
Poor Prognostic Factor ◽  
Muscle Cross Sectional Area ◽  
Total Muscle

Introduction Depletion of skeletal muscle is a poor prognostic factor for patients with various malignancies; however its significance for allogeneic hematopoietic cell transplantation (allo-HCT) in patients with hematological disease is unclear. Generally, muscle mass is measured by the methods established by the European Working Group on Sarcopenia in Older People, which require the use of dual energy X-ray absorptiometry or bioimpedance analysis, methods that are not performed in routine practice. Therefore, cross-sectional imaging using computed tomography (CT) has been suggested as an alternative method for analyzing muscle mass in clinical practice. Especially, lumbar total muscle cross-sectional area using CT, normalized for body height, which was named lumbar skeletal muscle mass index (SMI), is reported as an indicator of nutritional status, sarcopenia and cancer cachexia in patients with solid organ malignancy. Aims To clarify the usefulness of a pre-transplant lumber SMI as a prognostic indicator for allo-HCT patients. Methods Among 208 patients with hematological disease who underwent allo-HCT between 2006 and 2017 at our facility, 191 patients (95 males and 96 females) underwent CT scans for routine pre-transplant status assessment. Ninety patients had acute myeloid leukemia, 38 patients had acute lymphoblastic leukemia, 24 patients had myelodysplastic syndrome, 20 patients had malignant lymphoma, and 19 patients had other diseases. The median age of the patients was 42 years old (range: 16-66 years). Seventy-eight patients received myeloablative conditioning and the others received reduced intensity conditioning regimens. The number of patients in each HCT-comorbidity index (HCT-CI) risk group was as follows: low: 72, intermediate: 54 and high: 65. Axial images at the iliac crest were selected for analysis of lumber total muscle cross-sectional area (cm2). The rectus abdominus, psoas and paraspinal muscles were identified and quantified. Lumbar total muscle cross-sectional area was normalized for body height in meters squared (m2) and used to calculate lumbar SMI (cm2/m2). This study was performed in accordance with the Japanese Ethical Guidelines for Medical and Health Research Involving Humans and approved by the Ethical Committee of our facility. Results The median pre-transplant lumber SMI of the male patients was significantly higher than that of the female patients (42.7 (24.9-60.2) mm2/m2 vs. 31.9 (20.7-44.6) mm2/m2, p<0.01). We defined the cutoff value of lumber SMI as 42.7cm2/m2 for male and 31.9cm2/m2 for female patients. In the Kaplan-Meier estimate analysis, low lumber SMI was a significant poor prognostic factor for overall survival (p=0.016). In multivariate analysis using Cox regression model, adjusting for age, refined disease risk index, conditioning and HCT-CI, low lumber SMI was extracted as a significant poor prognostic factor for overall survival (hazard ratio 1.56, 95% confidence interval (CI) 1.03-2.36, p=0.036). By logistic regression analysis, adjusted odds ratio of 1-year non-relapse mortality for low lumber SMI was 2.47 (95% CI 1.13-5.41, p=0.024). Conclusion Low pre-transplant lumber SMI is a significant poor prognostic factor in allo-HCT, independent of other risk factors including HCT-CI and refined disease risk index in patients with hematological disease. It is affected by the high rate of non-relapse mortality in the early phase following allo-HCT in patients with low lumber SMI. Disclosures No relevant conflicts of interest to declare.

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