Unravelling the transcriptomic symphony of muscle ageing: key pathways and hub genes altered by ageing and caloric restriction in rat muscle revealed by RNA sequencing
Abstract Age-related muscle wasting, sarcopenia is an extensive loss of muscle mass and strength with age and a major cause of disability and accidents in the elderly. Mechanisms purported to be involved in muscle ageing and sarcopenia are numerous but poorly understood, necessitating deeper study....
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2025-01-01
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| Series: | BMC Genomics |
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| Online Access: | https://doi.org/10.1186/s12864-024-11051-1 |
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| author | Gulam Altab Brian J. Merry Charles W. Beckett Priyanka Raina Inês Lopes Katarzyna Goljanek-Whysall João Pedro de Magalhães |
| author_facet | Gulam Altab Brian J. Merry Charles W. Beckett Priyanka Raina Inês Lopes Katarzyna Goljanek-Whysall João Pedro de Magalhães |
| author_sort | Gulam Altab |
| collection | DOAJ |
| description | Abstract Age-related muscle wasting, sarcopenia is an extensive loss of muscle mass and strength with age and a major cause of disability and accidents in the elderly. Mechanisms purported to be involved in muscle ageing and sarcopenia are numerous but poorly understood, necessitating deeper study. Hence, we employed high-throughput RNA sequencing to survey the global changes in protein-coding gene expression occurring in skeletal muscle with age. Caloric restriction (CR) is a known prophylactic intervention against sarcopenia. Therefore, total RNA was isolated from the muscle tissue of both rats fed ad libitum and CR rats. RNA-seq data were subjected to Gene Ontology, pathway, co-expression, and interaction network analyses. This revealed the functional pathways most activated by both ageing and CR, as well as the key “hub” proteins involved in their activation. RNA-seq revealed 442 protein-coding genes to be upregulated and 377 to be downregulated in aged muscle, compared to young muscle. Upregulated genes were commonly involved in protein folding and immune responses; meanwhile, downregulated genes were often related to developmental biology. CR was found to suppress 69.7% and rescue 57.8% of the genes found to be upregulated and downregulated in aged muscle, respectively. In addition, CR uniquely upregulated 291 and downregulated 304 protein-coding genes. Hub genes implicated in both ageing and CR included Gc, Plg, Irf7, Ifit3, Usp18, Rsad2, Blm and RT1-A2, whilst those exclusively implicated in CR responses included Alb, Apoa1, Ambp, F2, Apoh, Orm1, Mx1, Oasl2 and Rtp4. Hub genes involved in ageing but unaffected by CR included Fgg, Fga, Fgb and Serpinc1. In conclusion, this comprehensive RNA sequencing study highlights gene expression patterns, hub genes and signalling pathways most affected by ageing in skeletal muscle. This data may provide the initial evidence for several targets for potential future therapeutic interventions against sarcopenia. |
| format | Article |
| id | doaj-art-5d47fd98ee7745b0b6eae9b6f3bd832e |
| institution | Kabale University |
| issn | 1471-2164 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj-art-5d47fd98ee7745b0b6eae9b6f3bd832e2025-01-19T12:11:35ZengBMCBMC Genomics1471-21642025-01-0126112210.1186/s12864-024-11051-1Unravelling the transcriptomic symphony of muscle ageing: key pathways and hub genes altered by ageing and caloric restriction in rat muscle revealed by RNA sequencingGulam Altab0Brian J. Merry1Charles W. Beckett2Priyanka Raina3Inês Lopes4Katarzyna Goljanek-Whysall5João Pedro de Magalhães6Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of LiverpoolInstitute of Integrative Biology, University of LiverpoolIntegrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of LiverpoolIntegrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of LiverpoolIntegrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of LiverpoolIntegrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of LiverpoolIntegrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of LiverpoolAbstract Age-related muscle wasting, sarcopenia is an extensive loss of muscle mass and strength with age and a major cause of disability and accidents in the elderly. Mechanisms purported to be involved in muscle ageing and sarcopenia are numerous but poorly understood, necessitating deeper study. Hence, we employed high-throughput RNA sequencing to survey the global changes in protein-coding gene expression occurring in skeletal muscle with age. Caloric restriction (CR) is a known prophylactic intervention against sarcopenia. Therefore, total RNA was isolated from the muscle tissue of both rats fed ad libitum and CR rats. RNA-seq data were subjected to Gene Ontology, pathway, co-expression, and interaction network analyses. This revealed the functional pathways most activated by both ageing and CR, as well as the key “hub” proteins involved in their activation. RNA-seq revealed 442 protein-coding genes to be upregulated and 377 to be downregulated in aged muscle, compared to young muscle. Upregulated genes were commonly involved in protein folding and immune responses; meanwhile, downregulated genes were often related to developmental biology. CR was found to suppress 69.7% and rescue 57.8% of the genes found to be upregulated and downregulated in aged muscle, respectively. In addition, CR uniquely upregulated 291 and downregulated 304 protein-coding genes. Hub genes implicated in both ageing and CR included Gc, Plg, Irf7, Ifit3, Usp18, Rsad2, Blm and RT1-A2, whilst those exclusively implicated in CR responses included Alb, Apoa1, Ambp, F2, Apoh, Orm1, Mx1, Oasl2 and Rtp4. Hub genes involved in ageing but unaffected by CR included Fgg, Fga, Fgb and Serpinc1. In conclusion, this comprehensive RNA sequencing study highlights gene expression patterns, hub genes and signalling pathways most affected by ageing in skeletal muscle. This data may provide the initial evidence for several targets for potential future therapeutic interventions against sarcopenia.https://doi.org/10.1186/s12864-024-11051-1SarcopeniaDietFunctional genomicsNutrigenomics |
| spellingShingle | Gulam Altab Brian J. Merry Charles W. Beckett Priyanka Raina Inês Lopes Katarzyna Goljanek-Whysall João Pedro de Magalhães Unravelling the transcriptomic symphony of muscle ageing: key pathways and hub genes altered by ageing and caloric restriction in rat muscle revealed by RNA sequencing BMC Genomics Sarcopenia Diet Functional genomics Nutrigenomics |
| title | Unravelling the transcriptomic symphony of muscle ageing: key pathways and hub genes altered by ageing and caloric restriction in rat muscle revealed by RNA sequencing |
| title_full | Unravelling the transcriptomic symphony of muscle ageing: key pathways and hub genes altered by ageing and caloric restriction in rat muscle revealed by RNA sequencing |
| title_fullStr | Unravelling the transcriptomic symphony of muscle ageing: key pathways and hub genes altered by ageing and caloric restriction in rat muscle revealed by RNA sequencing |
| title_full_unstemmed | Unravelling the transcriptomic symphony of muscle ageing: key pathways and hub genes altered by ageing and caloric restriction in rat muscle revealed by RNA sequencing |
| title_short | Unravelling the transcriptomic symphony of muscle ageing: key pathways and hub genes altered by ageing and caloric restriction in rat muscle revealed by RNA sequencing |
| title_sort | unravelling the transcriptomic symphony of muscle ageing key pathways and hub genes altered by ageing and caloric restriction in rat muscle revealed by rna sequencing |
| topic | Sarcopenia Diet Functional genomics Nutrigenomics |
| url | https://doi.org/10.1186/s12864-024-11051-1 |
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