Novel drug targets and molecular mechanisms for sarcopenia based on systems biology

Atakan Burak Ceyhan; Mehmet Ozcan; Woonghee Kim; Xiangyu Li; Ozlem Altay; Cheng Zhang; Adil Mardinoglu

doi:10.1016/j.biopha.2024.116920

Novel drug targets and molecular mechanisms for sarcopenia based on systems biology

Atakan Burak Ceyhan, Mehmet Ozcan, Woonghee Kim, Xiangyu Li, Ozlem Altay, Cheng Zhang, Adil Mardinoglu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Sarcopenia is a major public health concern among older adults, leading to disabilities, falls, fractures, and mortality. This study aimed to elucidate the pathophysiological mechanisms of sarcopenia and identify potential therapeutic targets using systems biology approaches. RNA-seq data from muscle biopsies of 24 sarcopenic and 29 healthy individuals from a previous cohort were analysed. Differential expression, gene set enrichment, gene co-expression network, and topology analyses were conducted to identify target genes implicated in sarcopenia pathogenesis, resulting in the selection of 6 hub genes (PDHX, AGL, SEMA6C, CASQ1, MYORG, and CCDC69). A drug repurposing approach was then employed to identify new pharmacological treatment options for sarcopenia (clofibric-acid, troglitazone, withaferin-a, palbociclib, MG-132, bortezomib). Finally, validation experiments in muscle cell line (C2C12) revealed MG-132 and troglitazone as promising candidates for sarcopenia treatment. Our approach, based on systems biology and drug repositioning, provides insight into the molecular mechanisms of sarcopenia and offers potential new treatment options using existing drugs.

Original language	English
Article number	116920
Journal	Biomedicine and Pharmacotherapy
Volume	176
Early online date	13 Jun 2024
DOIs	https://doi.org/10.1016/j.biopha.2024.116920
Publication status	Published - Jul 2024

Keywords

Co-expression network analysis
Differential expression analysis
Drug repurposing
Sarcopenia
System biology
Translational medicine

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10.1016/j.biopha.2024.116920

Novel drug targets and_CEYHAN_Publishedonline13Jun2024_GOLD_VoR (CC BY)Final published version, 9.68 MBLicence: CC BY

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title = "Novel drug targets and molecular mechanisms for sarcopenia based on systems biology",

abstract = "Sarcopenia is a major public health concern among older adults, leading to disabilities, falls, fractures, and mortality. This study aimed to elucidate the pathophysiological mechanisms of sarcopenia and identify potential therapeutic targets using systems biology approaches. RNA-seq data from muscle biopsies of 24 sarcopenic and 29 healthy individuals from a previous cohort were analysed. Differential expression, gene set enrichment, gene co-expression network, and topology analyses were conducted to identify target genes implicated in sarcopenia pathogenesis, resulting in the selection of 6 hub genes (PDHX, AGL, SEMA6C, CASQ1, MYORG, and CCDC69). A drug repurposing approach was then employed to identify new pharmacological treatment options for sarcopenia (clofibric-acid, troglitazone, withaferin-a, palbociclib, MG-132, bortezomib). Finally, validation experiments in muscle cell line (C2C12) revealed MG-132 and troglitazone as promising candidates for sarcopenia treatment. Our approach, based on systems biology and drug repositioning, provides insight into the molecular mechanisms of sarcopenia and offers potential new treatment options using existing drugs.",

keywords = "Co-expression network analysis, Differential expression analysis, Drug repurposing, Sarcopenia, System biology, Translational medicine",

author = "Ceyhan, {Atakan Burak} and Mehmet Ozcan and Woonghee Kim and Xiangyu Li and Ozlem Altay and Cheng Zhang and Adil Mardinoglu",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

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doi = "10.1016/j.biopha.2024.116920",

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AU - Ceyhan, Atakan Burak

AU - Ozcan, Mehmet

AU - Kim, Woonghee

AU - Li, Xiangyu

AU - Altay, Ozlem

AU - Zhang, Cheng

AU - Mardinoglu, Adil

PY - 2024/7

Y1 - 2024/7

N2 - Sarcopenia is a major public health concern among older adults, leading to disabilities, falls, fractures, and mortality. This study aimed to elucidate the pathophysiological mechanisms of sarcopenia and identify potential therapeutic targets using systems biology approaches. RNA-seq data from muscle biopsies of 24 sarcopenic and 29 healthy individuals from a previous cohort were analysed. Differential expression, gene set enrichment, gene co-expression network, and topology analyses were conducted to identify target genes implicated in sarcopenia pathogenesis, resulting in the selection of 6 hub genes (PDHX, AGL, SEMA6C, CASQ1, MYORG, and CCDC69). A drug repurposing approach was then employed to identify new pharmacological treatment options for sarcopenia (clofibric-acid, troglitazone, withaferin-a, palbociclib, MG-132, bortezomib). Finally, validation experiments in muscle cell line (C2C12) revealed MG-132 and troglitazone as promising candidates for sarcopenia treatment. Our approach, based on systems biology and drug repositioning, provides insight into the molecular mechanisms of sarcopenia and offers potential new treatment options using existing drugs.

AB - Sarcopenia is a major public health concern among older adults, leading to disabilities, falls, fractures, and mortality. This study aimed to elucidate the pathophysiological mechanisms of sarcopenia and identify potential therapeutic targets using systems biology approaches. RNA-seq data from muscle biopsies of 24 sarcopenic and 29 healthy individuals from a previous cohort were analysed. Differential expression, gene set enrichment, gene co-expression network, and topology analyses were conducted to identify target genes implicated in sarcopenia pathogenesis, resulting in the selection of 6 hub genes (PDHX, AGL, SEMA6C, CASQ1, MYORG, and CCDC69). A drug repurposing approach was then employed to identify new pharmacological treatment options for sarcopenia (clofibric-acid, troglitazone, withaferin-a, palbociclib, MG-132, bortezomib). Finally, validation experiments in muscle cell line (C2C12) revealed MG-132 and troglitazone as promising candidates for sarcopenia treatment. Our approach, based on systems biology and drug repositioning, provides insight into the molecular mechanisms of sarcopenia and offers potential new treatment options using existing drugs.

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KW - Differential expression analysis

KW - Drug repurposing

KW - Sarcopenia

KW - System biology

KW - Translational medicine

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JO - Biomedicine and Pharmacotherapy

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ER -

Novel drug targets and molecular mechanisms for sarcopenia based on systems biology

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