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...

Full description

Bibliographic Details
Main Authors: Zeinab Abdelrahman, Xiaosheng Wang, Daming Wang, Tianfang Zhang, Yue Zhang, Xuhua Wang, Zuobing Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2023.928285/full
_version_ 1827965916908879872
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.
first_indexed 2024-04-09T17:40:51Z
format Article
id doaj.art-9cd742e283b4495783e9cf55d6048a72
institution Directory Open Access Journal
issn 2296-858X
language English
last_indexed 2024-04-09T17:40:51Z
publishDate 2023-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Medicine
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
work_keys_str_mv AT zeinababdelrahman identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT zeinababdelrahman identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT zeinababdelrahman identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT xiaoshengwang identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT xiaoshengwang identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT damingwang identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT tianfangzhang identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT yuezhang identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT xuhuawang identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT xuhuawang identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT xuhuawang identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT xuhuawang identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia
AT zuobingchen identificationofnovelpathwaysandimmuneprofilesrelatedtosarcopenia