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Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans
Sarcopenia, characterized by age-related loss of muscle mass, strength, and decreased physical performance, is a growing public health challenge amid the rapidly ageing population. As there are no approved drugs that target sarcopenia, it has become increasingly urgent to identify promising pharmaco...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145476/ https://www.ncbi.nlm.nih.gov/pubmed/37111364 http://dx.doi.org/10.3390/ph16040607 |
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author | Liang, Shuang Liu, Danyang Xiao, Zhengwu Greenbaum, Jonathan Shen, Hui Xiao, Hongmei Deng, Hongwen |
author_facet | Liang, Shuang Liu, Danyang Xiao, Zhengwu Greenbaum, Jonathan Shen, Hui Xiao, Hongmei Deng, Hongwen |
author_sort | Liang, Shuang |
collection | PubMed |
description | Sarcopenia, characterized by age-related loss of muscle mass, strength, and decreased physical performance, is a growing public health challenge amid the rapidly ageing population. As there are no approved drugs that target sarcopenia, it has become increasingly urgent to identify promising pharmacological interventions. In this study, we conducted an integrative drug repurposing analysis utilizing three distinct approaches. Firstly, we analyzed skeletal muscle transcriptomic sequencing data in humans and mice using gene differential expression analysis, weighted gene co-expression analysis, and gene set enrichment analysis. Subsequently, we employed gene expression profile similarity assessment, hub gene expression reversal, and disease-related pathway enrichment to identify and repurpose candidate drugs, followed by the integration of findings with rank aggregation algorithms. Vorinostat, the top-ranking drug, was also validated in an in vitro study, which demonstrated its efficacy in promoting muscle fiber formation. Although still requiring further validation in animal models and human clinical trials, these results suggest a promising drug repurposing prospect in the treatment and prevention of sarcopenia. |
format | Online Article Text |
id | pubmed-10145476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101454762023-04-29 Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans Liang, Shuang Liu, Danyang Xiao, Zhengwu Greenbaum, Jonathan Shen, Hui Xiao, Hongmei Deng, Hongwen Pharmaceuticals (Basel) Article Sarcopenia, characterized by age-related loss of muscle mass, strength, and decreased physical performance, is a growing public health challenge amid the rapidly ageing population. As there are no approved drugs that target sarcopenia, it has become increasingly urgent to identify promising pharmacological interventions. In this study, we conducted an integrative drug repurposing analysis utilizing three distinct approaches. Firstly, we analyzed skeletal muscle transcriptomic sequencing data in humans and mice using gene differential expression analysis, weighted gene co-expression analysis, and gene set enrichment analysis. Subsequently, we employed gene expression profile similarity assessment, hub gene expression reversal, and disease-related pathway enrichment to identify and repurpose candidate drugs, followed by the integration of findings with rank aggregation algorithms. Vorinostat, the top-ranking drug, was also validated in an in vitro study, which demonstrated its efficacy in promoting muscle fiber formation. Although still requiring further validation in animal models and human clinical trials, these results suggest a promising drug repurposing prospect in the treatment and prevention of sarcopenia. MDPI 2023-04-18 /pmc/articles/PMC10145476/ /pubmed/37111364 http://dx.doi.org/10.3390/ph16040607 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liang, Shuang Liu, Danyang Xiao, Zhengwu Greenbaum, Jonathan Shen, Hui Xiao, Hongmei Deng, Hongwen Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans |
title | Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans |
title_full | Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans |
title_fullStr | Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans |
title_full_unstemmed | Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans |
title_short | Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans |
title_sort | repurposing approved drugs for sarcopenia based on transcriptomics data in humans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145476/ https://www.ncbi.nlm.nih.gov/pubmed/37111364 http://dx.doi.org/10.3390/ph16040607 |
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