Young bone marrow transplantation prevents aging‐related muscle atrophy in a senescence‐accelerated mouse prone 10 model

Abstract Background Young bone marrow transplantation (YBMT) has been shown to stimulate vascular regeneration in pathological conditions, including ageing. Here, we investigated the benefits and mechanisms of the preventive effects of YBMT on loss of muscle mass and function in a senescence‐associa...

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Main Authors: Aiko Inoue, Limei Piao, Xueling Yue, Zhe Huang, Lina Hu, Hongxian Wu, Xiangkun Meng, Wenhu Xu, Chenglin Yu, Takeshi Sasaki, Kohji Itakura, Hiroyuki Umegaki, Masafumi Kuzuya, Xian Wu Cheng
Format: Article
Language:English
Published: Wiley 2022-12-01
Series:Journal of Cachexia, Sarcopenia and Muscle
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Online Access:https://doi.org/10.1002/jcsm.13058
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author Aiko Inoue
Limei Piao
Xueling Yue
Zhe Huang
Lina Hu
Hongxian Wu
Xiangkun Meng
Wenhu Xu
Chenglin Yu
Takeshi Sasaki
Kohji Itakura
Hiroyuki Umegaki
Masafumi Kuzuya
Xian Wu Cheng
author_facet Aiko Inoue
Limei Piao
Xueling Yue
Zhe Huang
Lina Hu
Hongxian Wu
Xiangkun Meng
Wenhu Xu
Chenglin Yu
Takeshi Sasaki
Kohji Itakura
Hiroyuki Umegaki
Masafumi Kuzuya
Xian Wu Cheng
author_sort Aiko Inoue
collection DOAJ
description Abstract Background Young bone marrow transplantation (YBMT) has been shown to stimulate vascular regeneration in pathological conditions, including ageing. Here, we investigated the benefits and mechanisms of the preventive effects of YBMT on loss of muscle mass and function in a senescence‐associated mouse prone 10 (SAMP10) model, with a special focus on the role of growth differentiation factor 11 (GDF‐11). Methods Nine‐week‐old male SAMP10 mice were randomly assigned to a non‐YBMT group (n = 6) and a YBMT group (n = 7) that received the bone marrow of 8‐week‐old C57BL/6 mice. Results Compared to the non‐YBMT mice, the YBMT mice showed the following significant increases (all P < 0.05 in 6–7 mice): endurance capacity (>61.3%); grip strength (>37.9%), percentage of slow myosin heavy chain fibres (>14.9–15.9%). The YBMT also increased the amounts of proteins or mRNAs for insulin receptor substrate 1, p‐Akt, p‐extracellular signal‐regulated protein kinase1/2, p‐mammalian target of rapamycin, Bcl‐2, peroxisom proliferator‐activated receptor‐γ coactivator (PGC‐1α), plus cytochrome c oxidase IV and the numbers of proliferating cells (n = 5–7, P < 0.05) and CD34+/integrin‐α7+ muscle stem cells (n = 5–6, P < 0.05). The YMBT significantly decreased the levels of gp91phox, caspase‐9 proteins and apoptotic cells (n = 5–7, P < 0.05) in both muscles; these beneficial changes were diminished by the blocking of GDF‐11 (n = 5–6, P < 0.05). An administration of mouse recombinant GDF‐11 improved the YBMT‐mediated muscle benefits (n = 5–6, P < 0.05). Cell therapy with young bone marrow from green fluorescent protein (GFP) transgenic mice exhibited GFP+ myofibres in aged muscle tissues. Conclusions These findings suggest that YBMT can prevent muscle wasting and dysfunction by mitigating apoptosis and proliferation via a modulation of GDF‐11 signalling and mitochondrial dysfunction in SAMP10 mice.
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spelling doaj.art-52afd5e80d20459fb132da46019aed912022-12-22T04:41:39ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092022-12-011363078309010.1002/jcsm.13058Young bone marrow transplantation prevents aging‐related muscle atrophy in a senescence‐accelerated mouse prone 10 modelAiko Inoue0Limei Piao1Xueling Yue2Zhe Huang3Lina Hu4Hongxian Wu5Xiangkun Meng6Wenhu Xu7Chenglin Yu8Takeshi Sasaki9Kohji Itakura10Hiroyuki Umegaki11Masafumi Kuzuya12Xian Wu Cheng13Institute of Innovation for Future Society Nagoya University Graduate School of Medicine Nagoya Aichiken JapanDepartment of Cardiology and Hypertension, Jilin Provincial Key Laboratory of Stress and Cardiovascular Disease Yanbian University Hospital Yanji Jilin PR ChinaDepartment of Cardiology and Hypertension, Jilin Provincial Key Laboratory of Stress and Cardiovascular Disease Yanbian University Hospital Yanji Jilin PR ChinaDepartment of Human Cord Applied Cell Therapy Nagoya University Graduate School of Medicine Nagoya Aichiken JapanDepartment of Public Health Guilin Medical College Guilin Guangxi PR ChinaShanghai Institute of Cardiovascular Disease, Zhongshan Hospital Fudan University Shanghai PR ChinaDepartment of Community Healthcare and Geriatrics Nagoya University Graduate School of Medicine Nagoya Aichiken JapanDepartment of Cardiology and Hypertension, Jilin Provincial Key Laboratory of Stress and Cardiovascular Disease Yanbian University Hospital Yanji Jilin PR ChinaDepartment of Cardiology and Hypertension, Jilin Provincial Key Laboratory of Stress and Cardiovascular Disease Yanbian University Hospital Yanji Jilin PR ChinaDepartment of Anatomy and Neuroscience Hamamatsu University School of Medicine Hamamatsu Shizuokaken JapanDivision for Medical Research Engineering Nagoya University Graduate School of Medicine Nagoya Aichiken JapanInstitute of Innovation for Future Society Nagoya University Graduate School of Medicine Nagoya Aichiken JapanInstitute of Innovation for Future Society Nagoya University Graduate School of Medicine Nagoya Aichiken JapanDepartment of Cardiology and Hypertension, Jilin Provincial Key Laboratory of Stress and Cardiovascular Disease Yanbian University Hospital Yanji Jilin PR ChinaAbstract Background Young bone marrow transplantation (YBMT) has been shown to stimulate vascular regeneration in pathological conditions, including ageing. Here, we investigated the benefits and mechanisms of the preventive effects of YBMT on loss of muscle mass and function in a senescence‐associated mouse prone 10 (SAMP10) model, with a special focus on the role of growth differentiation factor 11 (GDF‐11). Methods Nine‐week‐old male SAMP10 mice were randomly assigned to a non‐YBMT group (n = 6) and a YBMT group (n = 7) that received the bone marrow of 8‐week‐old C57BL/6 mice. Results Compared to the non‐YBMT mice, the YBMT mice showed the following significant increases (all P < 0.05 in 6–7 mice): endurance capacity (>61.3%); grip strength (>37.9%), percentage of slow myosin heavy chain fibres (>14.9–15.9%). The YBMT also increased the amounts of proteins or mRNAs for insulin receptor substrate 1, p‐Akt, p‐extracellular signal‐regulated protein kinase1/2, p‐mammalian target of rapamycin, Bcl‐2, peroxisom proliferator‐activated receptor‐γ coactivator (PGC‐1α), plus cytochrome c oxidase IV and the numbers of proliferating cells (n = 5–7, P < 0.05) and CD34+/integrin‐α7+ muscle stem cells (n = 5–6, P < 0.05). The YMBT significantly decreased the levels of gp91phox, caspase‐9 proteins and apoptotic cells (n = 5–7, P < 0.05) in both muscles; these beneficial changes were diminished by the blocking of GDF‐11 (n = 5–6, P < 0.05). An administration of mouse recombinant GDF‐11 improved the YBMT‐mediated muscle benefits (n = 5–6, P < 0.05). Cell therapy with young bone marrow from green fluorescent protein (GFP) transgenic mice exhibited GFP+ myofibres in aged muscle tissues. Conclusions These findings suggest that YBMT can prevent muscle wasting and dysfunction by mitigating apoptosis and proliferation via a modulation of GDF‐11 signalling and mitochondrial dysfunction in SAMP10 mice.https://doi.org/10.1002/jcsm.13058AgingSarcopeniaMouse modelBone marrow transplantationMuscle stem cellSAMP10
spellingShingle Aiko Inoue
Limei Piao
Xueling Yue
Zhe Huang
Lina Hu
Hongxian Wu
Xiangkun Meng
Wenhu Xu
Chenglin Yu
Takeshi Sasaki
Kohji Itakura
Hiroyuki Umegaki
Masafumi Kuzuya
Xian Wu Cheng
Young bone marrow transplantation prevents aging‐related muscle atrophy in a senescence‐accelerated mouse prone 10 model
Journal of Cachexia, Sarcopenia and Muscle
Aging
Sarcopenia
Mouse model
Bone marrow transplantation
Muscle stem cell
SAMP10
title Young bone marrow transplantation prevents aging‐related muscle atrophy in a senescence‐accelerated mouse prone 10 model
title_full Young bone marrow transplantation prevents aging‐related muscle atrophy in a senescence‐accelerated mouse prone 10 model
title_fullStr Young bone marrow transplantation prevents aging‐related muscle atrophy in a senescence‐accelerated mouse prone 10 model
title_full_unstemmed Young bone marrow transplantation prevents aging‐related muscle atrophy in a senescence‐accelerated mouse prone 10 model
title_short Young bone marrow transplantation prevents aging‐related muscle atrophy in a senescence‐accelerated mouse prone 10 model
title_sort young bone marrow transplantation prevents aging related muscle atrophy in a senescence accelerated mouse prone 10 model
topic Aging
Sarcopenia
Mouse model
Bone marrow transplantation
Muscle stem cell
SAMP10
url https://doi.org/10.1002/jcsm.13058
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