AUTHOR=Abdelrahman Zeinab , Wang Xiaosheng , Wang Daming , Zhang Tianfang , Zhang Yue , Wang Xuhua , Chen Zuobing 

TITLE=Identification of novel pathways and immune profiles related to sarcopenia

JOURNAL=Frontiers in Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.928285

DOI=10.3389/fmed.2023.928285

ISSN=2296-858X

ABSTRACT=<sec><title>Introduction</title><p>Sarcopenia is a progressive deterioration of skeletal muscle mass strength and function.</p></sec><sec><title>Methods</title><p>To 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.</p></sec><sec><title>Results</title><p>We 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, <italic>TTC39DP, SLURP1, LCE1C, PTCD2P1</italic>, and <italic>OR7E109P</italic>, were expressed between S patients and healthy controls. <italic>SLURP1</italic> and <italic>LCE1C</italic> 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: <italic>POSTN</italic> and <italic>SLURP1</italic>. <italic>TTC39DP</italic> upregulation was associated with a better prognosis and stronger immune profile in S patients. The upregulation of <italic>SLURP1</italic> and <italic>LCE1C</italic> was associated with a worse prognosis and weaker immune profile.</p></sec><sec><title>Conclusion</title><p>This study provides new insight into sarcopenia's cellular and immunological prospects and evaluates the age and sarcopenia-related modifications of skeletal muscle.</p></sec>