Identification of novel pathways and immune profiles related to sarcopenia
IntroductionSarcopenia is a progressive deterioration of skeletal muscle mass strength and function.MethodsTo uncover the underlying cellular and biological mechanisms, we studied the association between sarcopenia's three stages and the patient's ethnicity, identified a gene regulatory ne...
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Frontiers Media S.A.
2023-04-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.928285/full |
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author | Zeinab Abdelrahman Zeinab Abdelrahman Zeinab Abdelrahman Xiaosheng Wang Xiaosheng Wang Daming Wang Tianfang Zhang Yue Zhang Xuhua Wang Xuhua Wang Xuhua Wang Xuhua Wang Zuobing Chen |
author_facet | Zeinab Abdelrahman Zeinab Abdelrahman Zeinab Abdelrahman Xiaosheng Wang Xiaosheng Wang Daming Wang Tianfang Zhang Yue Zhang Xuhua Wang Xuhua Wang Xuhua Wang Xuhua Wang Zuobing Chen |
author_sort | Zeinab Abdelrahman |
collection | DOAJ |
description | IntroductionSarcopenia is a progressive deterioration of skeletal muscle mass strength and function.MethodsTo uncover the underlying cellular and biological mechanisms, we studied the association between sarcopenia's three stages and the patient's ethnicity, identified a gene regulatory network based on motif enrichment in the upregulated gene set of sarcopenia, and compared the immunological landscape among sarcopenia stages.ResultsWe found that sarcopenia (S) was associated with GnRH, neurotrophin, Rap1, Ras, and p53 signaling pathways. Low muscle mass (LMM) patients showed activated pathways of VEGF signaling, B-cell receptor signaling, ErbB signaling, and T-cell receptor signaling. Low muscle mass and physical performance (LMM_LP) patients showed lower enrichment scores in B-cell receptor signaling, apoptosis, HIF-1 signaling, and the adaptive immune response pathways. Five common genes among DEGs and the elastic net regression model, TTC39DP, SLURP1, LCE1C, PTCD2P1, and OR7E109P, were expressed between S patients and healthy controls. SLURP1 and LCE1C showed the highest expression levels among sarcopenic Chinese descent than Caucasians and Afro-Caribbeans. Gene regulatory analysis of top upregulated genes in S patients yielded a top-scoring regulon containing GATA1, GATA2, and GATA3 as master regulators and nine predicted direct target genes. Two genes were associated with locomotion: POSTN and SLURP1. TTC39DP upregulation was associated with a better prognosis and stronger immune profile in S patients. The upregulation of SLURP1 and LCE1C was associated with a worse prognosis and weaker immune profile.ConclusionThis study provides new insight into sarcopenia's cellular and immunological prospects and evaluates the age and sarcopenia-related modifications of skeletal muscle. |
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language | English |
last_indexed | 2024-04-09T17:40:51Z |
publishDate | 2023-04-01 |
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spelling | doaj.art-9cd742e283b4495783e9cf55d6048a722023-04-17T05:31:03ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-04-011010.3389/fmed.2023.928285928285Identification of novel pathways and immune profiles related to sarcopeniaZeinab Abdelrahman0Zeinab Abdelrahman1Zeinab Abdelrahman2Xiaosheng Wang3Xiaosheng Wang4Daming Wang5Tianfang Zhang6Yue Zhang7Xuhua Wang8Xuhua Wang9Xuhua Wang10Xuhua Wang11Zuobing Chen12Department of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaNHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain–Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Neurobiology and Department of Orthopedics, Zhejiang University School of Medicine, 2nd Affiliated Hospital, Hangzhou, Zhejiang, ChinaBiomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaBig Data Research Institute, China Pharmaceutical University, Nanjing, ChinaDepartment of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaShenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, ChinaDepartment of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaNHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain–Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Neurobiology and Department of Orthopedics, Zhejiang University School of Medicine, 2nd Affiliated Hospital, Hangzhou, Zhejiang, ChinaCo-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, ChinaDepartment of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaIntroductionSarcopenia is a progressive deterioration of skeletal muscle mass strength and function.MethodsTo uncover the underlying cellular and biological mechanisms, we studied the association between sarcopenia's three stages and the patient's ethnicity, identified a gene regulatory network based on motif enrichment in the upregulated gene set of sarcopenia, and compared the immunological landscape among sarcopenia stages.ResultsWe found that sarcopenia (S) was associated with GnRH, neurotrophin, Rap1, Ras, and p53 signaling pathways. Low muscle mass (LMM) patients showed activated pathways of VEGF signaling, B-cell receptor signaling, ErbB signaling, and T-cell receptor signaling. Low muscle mass and physical performance (LMM_LP) patients showed lower enrichment scores in B-cell receptor signaling, apoptosis, HIF-1 signaling, and the adaptive immune response pathways. Five common genes among DEGs and the elastic net regression model, TTC39DP, SLURP1, LCE1C, PTCD2P1, and OR7E109P, were expressed between S patients and healthy controls. SLURP1 and LCE1C showed the highest expression levels among sarcopenic Chinese descent than Caucasians and Afro-Caribbeans. Gene regulatory analysis of top upregulated genes in S patients yielded a top-scoring regulon containing GATA1, GATA2, and GATA3 as master regulators and nine predicted direct target genes. Two genes were associated with locomotion: POSTN and SLURP1. TTC39DP upregulation was associated with a better prognosis and stronger immune profile in S patients. The upregulation of SLURP1 and LCE1C was associated with a worse prognosis and weaker immune profile.ConclusionThis study provides new insight into sarcopenia's cellular and immunological prospects and evaluates the age and sarcopenia-related modifications of skeletal muscle.https://www.frontiersin.org/articles/10.3389/fmed.2023.928285/fullsarcopenialow muscle masslow physical performanceimmunologypathway analysisbioinformatics |
spellingShingle | Zeinab Abdelrahman Zeinab Abdelrahman Zeinab Abdelrahman Xiaosheng Wang Xiaosheng Wang Daming Wang Tianfang Zhang Yue Zhang Xuhua Wang Xuhua Wang Xuhua Wang Xuhua Wang Zuobing Chen Identification of novel pathways and immune profiles related to sarcopenia Frontiers in Medicine sarcopenia low muscle mass low physical performance immunology pathway analysis bioinformatics |
title | Identification of novel pathways and immune profiles related to sarcopenia |
title_full | Identification of novel pathways and immune profiles related to sarcopenia |
title_fullStr | Identification of novel pathways and immune profiles related to sarcopenia |
title_full_unstemmed | Identification of novel pathways and immune profiles related to sarcopenia |
title_short | Identification of novel pathways and immune profiles related to sarcopenia |
title_sort | identification of novel pathways and immune profiles related to sarcopenia |
topic | sarcopenia low muscle mass low physical performance immunology pathway analysis bioinformatics |
url | https://www.frontiersin.org/articles/10.3389/fmed.2023.928285/full |
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