Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse model
The elderly population, who have increased susceptibility to severe outcomes, have been particularly impacted by the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to a global health crisis. However, definitive parameters or mechan...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Virulence |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2025.2487671 |
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| author | Li Ma Xian Lin Meng Xu Xianliang Ke Di Liu Quanjiao Chen |
| author_facet | Li Ma Xian Lin Meng Xu Xianliang Ke Di Liu Quanjiao Chen |
| author_sort | Li Ma |
| collection | DOAJ |
| description | The elderly population, who have increased susceptibility to severe outcomes, have been particularly impacted by the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to a global health crisis. However, definitive parameters or mechanisms underlying the severity of COVID-19 in elderly people remain unclear. Thus, this study seeks to elucidate the mechanism behind the increased vulnerability of elderly individuals to severe COVID-19. We employed an aged mouse model with a mouse-adapted SARS-CoV-2 strain to mimic the severe symptoms observed in elderly patients with COVID-19. Comprehensive analyses of the whole lung were performed using transcriptome and proteome sequencing, comparing data from aged and young mice. For transcriptome analysis, bulk RNA sequencing was conducted using an Illumina sequencing platform. Proteomic analysis was performed using mass spectrometry following protein extraction, digestion, and peptide labelling. We analysed the transcriptome and proteome profiles of young and aged mice and discovered that aged mice exhibited elevated baseline levels of inflammation and tissue damage repair. After SARS-CoV-2 infection, aged mice showed increased antiviral and inflammatory responses; however, these responses were weaker than those in young mice, with significant complement and coagulation cascade responses. In summary, our study demonstrates that the increased vulnerability of the elderly to severe COVID-19 may be attributed to an attenuated antiviral response and the overactivation of complement and coagulation cascades. Future research on antiviral and inflammatory responses is likely to yield treatments that reduce the severity of viral respiratory diseases in the elderly. |
| format | Article |
| id | doaj-art-07ea273191ac48f99bb8522f39c3d192 |
| institution | OA Journals |
| issn | 2150-5594 2150-5608 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj-art-07ea273191ac48f99bb8522f39c3d1922025-08-20T02:16:10ZengTaylor & Francis GroupVirulence2150-55942150-56082025-12-0116110.1080/21505594.2025.2487671Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse modelLi Ma0Xian Lin1Meng Xu2Xianliang Ke3Di Liu4Quanjiao Chen5State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaThe elderly population, who have increased susceptibility to severe outcomes, have been particularly impacted by the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to a global health crisis. However, definitive parameters or mechanisms underlying the severity of COVID-19 in elderly people remain unclear. Thus, this study seeks to elucidate the mechanism behind the increased vulnerability of elderly individuals to severe COVID-19. We employed an aged mouse model with a mouse-adapted SARS-CoV-2 strain to mimic the severe symptoms observed in elderly patients with COVID-19. Comprehensive analyses of the whole lung were performed using transcriptome and proteome sequencing, comparing data from aged and young mice. For transcriptome analysis, bulk RNA sequencing was conducted using an Illumina sequencing platform. Proteomic analysis was performed using mass spectrometry following protein extraction, digestion, and peptide labelling. We analysed the transcriptome and proteome profiles of young and aged mice and discovered that aged mice exhibited elevated baseline levels of inflammation and tissue damage repair. After SARS-CoV-2 infection, aged mice showed increased antiviral and inflammatory responses; however, these responses were weaker than those in young mice, with significant complement and coagulation cascade responses. In summary, our study demonstrates that the increased vulnerability of the elderly to severe COVID-19 may be attributed to an attenuated antiviral response and the overactivation of complement and coagulation cascades. Future research on antiviral and inflammatory responses is likely to yield treatments that reduce the severity of viral respiratory diseases in the elderly.https://www.tandfonline.com/doi/10.1080/21505594.2025.2487671SARS-CoV-2aged micetranscriptomeproteomecomplement activationimmune response |
| spellingShingle | Li Ma Xian Lin Meng Xu Xianliang Ke Di Liu Quanjiao Chen Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse model Virulence SARS-CoV-2 aged mice transcriptome proteome complement activation immune response |
| title | Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse model |
| title_full | Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse model |
| title_fullStr | Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse model |
| title_full_unstemmed | Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse model |
| title_short | Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse model |
| title_sort | exploring the biological mechanisms of severe covid 19 in the elderly insights from an aged mouse model |
| topic | SARS-CoV-2 aged mice transcriptome proteome complement activation immune response |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2025.2487671 |
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