The regulation of microglia by aging and autophagy in multiple sclerosis
Multiple sclerosis (MS) is an inflammatory disease that is often characterized by the development of irreversible clinical disability. Age is a strong risk factor that is strongly associated with the clinical course and progression of MS. Several lines of evidence suggest that with aging, microglia...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825002117 |
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| author | Xiying Wang Ye Sun Haojun Yu Chunran Xue Xuzhong Pei Yi Chen Yangtai Guan |
| author_facet | Xiying Wang Ye Sun Haojun Yu Chunran Xue Xuzhong Pei Yi Chen Yangtai Guan |
| author_sort | Xiying Wang |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is an inflammatory disease that is often characterized by the development of irreversible clinical disability. Age is a strong risk factor that is strongly associated with the clinical course and progression of MS. Several lines of evidence suggest that with aging, microglia have an aging-related gene expression signature and are close to disease-associated microglia (DAM), which exhibit decreased phagocytosis but increased production of inflammatory factors. The gene expression signatures of microglia in MS overlap with those in aging, inflammation and DAM. Moreover, the clearance of damaged myelin by microglia is impaired in the aged brain. Autophagy is a cellular process that decreases in activity with age. In this review, we provide an overview of the role of autophagy and aging in MS. We describe the impact of autophagy and aging on microglial activation in MS and the molecules involved in autophagy and aging, which are related to the phagocytosis and activation of microglia. We propose that a decrease in autophagy in microglia occurs with aging, leading to a decrease in phagocytosis. Decreases in phagocytosis and increases in the production of inflammatory factors by microglia contribute to chronic inflammation in the aged brain and disease progression in MS. Thus, the modulation of autophagy in microglia serves as a potential therapeutic target for MS. |
| format | Article |
| id | doaj-art-bdefb87b56d642f7a20d07edf8398fe4 |
| institution | OA Journals |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-bdefb87b56d642f7a20d07edf8398fe42025-08-20T02:02:01ZengElsevierPharmacological Research1096-11862025-06-0121610778610.1016/j.phrs.2025.107786The regulation of microglia by aging and autophagy in multiple sclerosisXiying Wang0Ye Sun1Haojun Yu2Chunran Xue3Xuzhong Pei4Yi Chen5Yangtai Guan6Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCorresponding author.; Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaMultiple sclerosis (MS) is an inflammatory disease that is often characterized by the development of irreversible clinical disability. Age is a strong risk factor that is strongly associated with the clinical course and progression of MS. Several lines of evidence suggest that with aging, microglia have an aging-related gene expression signature and are close to disease-associated microglia (DAM), which exhibit decreased phagocytosis but increased production of inflammatory factors. The gene expression signatures of microglia in MS overlap with those in aging, inflammation and DAM. Moreover, the clearance of damaged myelin by microglia is impaired in the aged brain. Autophagy is a cellular process that decreases in activity with age. In this review, we provide an overview of the role of autophagy and aging in MS. We describe the impact of autophagy and aging on microglial activation in MS and the molecules involved in autophagy and aging, which are related to the phagocytosis and activation of microglia. We propose that a decrease in autophagy in microglia occurs with aging, leading to a decrease in phagocytosis. Decreases in phagocytosis and increases in the production of inflammatory factors by microglia contribute to chronic inflammation in the aged brain and disease progression in MS. Thus, the modulation of autophagy in microglia serves as a potential therapeutic target for MS.http://www.sciencedirect.com/science/article/pii/S1043661825002117MicrogliaMultiple sclerosisAutophagyAgingAutophagic targets in multiple sclerosis |
| spellingShingle | Xiying Wang Ye Sun Haojun Yu Chunran Xue Xuzhong Pei Yi Chen Yangtai Guan The regulation of microglia by aging and autophagy in multiple sclerosis Pharmacological Research Microglia Multiple sclerosis Autophagy Aging Autophagic targets in multiple sclerosis |
| title | The regulation of microglia by aging and autophagy in multiple sclerosis |
| title_full | The regulation of microglia by aging and autophagy in multiple sclerosis |
| title_fullStr | The regulation of microglia by aging and autophagy in multiple sclerosis |
| title_full_unstemmed | The regulation of microglia by aging and autophagy in multiple sclerosis |
| title_short | The regulation of microglia by aging and autophagy in multiple sclerosis |
| title_sort | regulation of microglia by aging and autophagy in multiple sclerosis |
| topic | Microglia Multiple sclerosis Autophagy Aging Autophagic targets in multiple sclerosis |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825002117 |
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