TY - JOUR
T1 - Identification of candidate genes and proteins in aging skeletal muscle (sarcopenia) using gene expression and structural analysis
AU - Shafiee, Gita
AU - Asgari, Yazdan
AU - Soltani, Akbar
AU - Larijani, Bagher
AU - Heshmat, Ramin
N1 - Publisher Copyright:
© 2018 Shafiee et al.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Sarcopenia is an age-related disease characterized by the loss of muscle mass and muscle function. A proper understanding of its pathogenesis and mechanisms may lead to new strategies for diagnosis and treatment of the disease. This study aims to discover the underlying genes, proteins, and pathways associated with sarcopenia in both genders. Integrated analysis of microarray datasets has been performed to identify differentially expressed genes (DEGs) between old and young skeletal muscles. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then performed to uncover the functions of the DEGs. Moreover, a protein-protein interaction (PPI) network was constructed based on the DEGs. We have identified 41,715 DEGs, including 19 downregulated and 41,696 upregulated ones, in men. Among women, 3,015 DEGs have been found, with 2,874 of them being upregulated and 141 downregulated genes. Among the top up-regulated and downregulated genes, the ribosome biogenesis genes and genes involved in lipid storage may be closely related to aging muscles in men and women respectively. Also, the DEGs were enriched in the pathways including those of ribosome and Peroxisome proliferator-activated receptor (PPAR) in men and women, respectively. In the PPI network, Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), Cullin 3 (CUL3) and P53 have been identified as significant hub proteins in both genders. Using the integrated analysis of multiple gene expression profiles, we propose that the ribosome biogenesis genes and those involved in lipid storage would be promising markers for sarcopenia in men and women, respectively. In the reconstructed PPI network, neurotrophic factors expressed in skeletal muscle are essential for motoneuron survival and muscle fiber innervation during development. Cullin E3 ubiquitin ligase (Cul3) is an important component of the ubiquitin-proteasome system-it regulates the proteolysis. P53 is recognized as a central regulator of the cell cycle and apoptosis. These proteins, which have been identified as the most significant hubs, may be involved in aging muscle and sarcopenia.
AB - Sarcopenia is an age-related disease characterized by the loss of muscle mass and muscle function. A proper understanding of its pathogenesis and mechanisms may lead to new strategies for diagnosis and treatment of the disease. This study aims to discover the underlying genes, proteins, and pathways associated with sarcopenia in both genders. Integrated analysis of microarray datasets has been performed to identify differentially expressed genes (DEGs) between old and young skeletal muscles. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then performed to uncover the functions of the DEGs. Moreover, a protein-protein interaction (PPI) network was constructed based on the DEGs. We have identified 41,715 DEGs, including 19 downregulated and 41,696 upregulated ones, in men. Among women, 3,015 DEGs have been found, with 2,874 of them being upregulated and 141 downregulated genes. Among the top up-regulated and downregulated genes, the ribosome biogenesis genes and genes involved in lipid storage may be closely related to aging muscles in men and women respectively. Also, the DEGs were enriched in the pathways including those of ribosome and Peroxisome proliferator-activated receptor (PPAR) in men and women, respectively. In the PPI network, Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), Cullin 3 (CUL3) and P53 have been identified as significant hub proteins in both genders. Using the integrated analysis of multiple gene expression profiles, we propose that the ribosome biogenesis genes and those involved in lipid storage would be promising markers for sarcopenia in men and women, respectively. In the reconstructed PPI network, neurotrophic factors expressed in skeletal muscle are essential for motoneuron survival and muscle fiber innervation during development. Cullin E3 ubiquitin ligase (Cul3) is an important component of the ubiquitin-proteasome system-it regulates the proteolysis. P53 is recognized as a central regulator of the cell cycle and apoptosis. These proteins, which have been identified as the most significant hubs, may be involved in aging muscle and sarcopenia.
KW - Aging
KW - Sarcopenia
KW - Skeletal muscle
KW - Structural analysis
UR - http://www.scopus.com/inward/record.url?scp=85052904856&partnerID=8YFLogxK
U2 - 10.7717/peerj.5239
DO - 10.7717/peerj.5239
M3 - Article
AN - SCOPUS:85052904856
SN - 2167-8359
VL - 2018
JO - PeerJ
JF - PeerJ
IS - 9
M1 - e5239
ER -