Novel drug targets and molecular mechanisms for sarcopenia based on systems biology.
Biomed Pharmacother
; 176: 116920, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38876054
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biología de Sistemas
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Sarcopenia
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Reposicionamiento de Medicamentos
Límite:
Aged
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido