Meta-epigenetic shifts in T cell aging and aging-related dysfunction
Abstract Epigenetic regulation, including DNA methylation and histone modifications, play a pivotal role in shaping T cell functionality throughout life. With aging, these epigenetic changes profoundly affect gene expression, altering T cell plasticity, activation, and differentiation. These modific...
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BMC
2025-05-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | https://doi.org/10.1186/s12929-025-01146-6 |
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| author | Lorène Rousseau Karina L. Hajdu Ping-Chih Ho |
| author_facet | Lorène Rousseau Karina L. Hajdu Ping-Chih Ho |
| author_sort | Lorène Rousseau |
| collection | DOAJ |
| description | Abstract Epigenetic regulation, including DNA methylation and histone modifications, play a pivotal role in shaping T cell functionality throughout life. With aging, these epigenetic changes profoundly affect gene expression, altering T cell plasticity, activation, and differentiation. These modifications contribute significantly to immunosenescence, increasing susceptibility to infections, cancer, and autoimmune diseases. In CD8⁺ T cells, chromatin closure at key regulatory regions suppresses activation and migration, while chromatin opening in pro-inflammatory gene loci amplifies inflammation. These changes drive terminal differentiation, characterized by increased expression of senescence-associated markers, impaired migration and loss of epigenetic plasticity. CD4⁺ T cells experience fewer but critical epigenetic alterations, including disrupted pathways, a skewed Th1/Th2 balance, and reduced Treg functionality. These epigenetic changes, compounded by metabolic dysfunctions, such as mitochondrial deficiency and oxidative stress, impair T-cell adaptability and resilience in the aging organism. Therefore, understanding the interplay between epigenetic and metabolic factors in T cell aging offers promising therapeutic opportunities to mitigate immunosenescence and enhance immune function in aging populations. This review explores the interplay between DNA methylation, histone alterations, and metabolic changes underlying T cell aging. |
| format | Article |
| id | doaj-art-cc896299f5104e6eb9df352e2b7f90d7 |
| institution | Kabale University |
| issn | 1423-0127 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj-art-cc896299f5104e6eb9df352e2b7f90d72025-08-20T03:48:18ZengBMCJournal of Biomedical Science1423-01272025-05-0132111310.1186/s12929-025-01146-6Meta-epigenetic shifts in T cell aging and aging-related dysfunctionLorène Rousseau0Karina L. Hajdu1Ping-Chih Ho2Department of Fundamental Oncology, University of LausanneDepartment of Fundamental Oncology, University of LausanneDepartment of Fundamental Oncology, University of LausanneAbstract Epigenetic regulation, including DNA methylation and histone modifications, play a pivotal role in shaping T cell functionality throughout life. With aging, these epigenetic changes profoundly affect gene expression, altering T cell plasticity, activation, and differentiation. These modifications contribute significantly to immunosenescence, increasing susceptibility to infections, cancer, and autoimmune diseases. In CD8⁺ T cells, chromatin closure at key regulatory regions suppresses activation and migration, while chromatin opening in pro-inflammatory gene loci amplifies inflammation. These changes drive terminal differentiation, characterized by increased expression of senescence-associated markers, impaired migration and loss of epigenetic plasticity. CD4⁺ T cells experience fewer but critical epigenetic alterations, including disrupted pathways, a skewed Th1/Th2 balance, and reduced Treg functionality. These epigenetic changes, compounded by metabolic dysfunctions, such as mitochondrial deficiency and oxidative stress, impair T-cell adaptability and resilience in the aging organism. Therefore, understanding the interplay between epigenetic and metabolic factors in T cell aging offers promising therapeutic opportunities to mitigate immunosenescence and enhance immune function in aging populations. This review explores the interplay between DNA methylation, histone alterations, and metabolic changes underlying T cell aging.https://doi.org/10.1186/s12929-025-01146-6ImmunosenescenceT cell agingDNA methylationImmune agingT cell metabolismT cell dysfunction |
| spellingShingle | Lorène Rousseau Karina L. Hajdu Ping-Chih Ho Meta-epigenetic shifts in T cell aging and aging-related dysfunction Journal of Biomedical Science Immunosenescence T cell aging DNA methylation Immune aging T cell metabolism T cell dysfunction |
| title | Meta-epigenetic shifts in T cell aging and aging-related dysfunction |
| title_full | Meta-epigenetic shifts in T cell aging and aging-related dysfunction |
| title_fullStr | Meta-epigenetic shifts in T cell aging and aging-related dysfunction |
| title_full_unstemmed | Meta-epigenetic shifts in T cell aging and aging-related dysfunction |
| title_short | Meta-epigenetic shifts in T cell aging and aging-related dysfunction |
| title_sort | meta epigenetic shifts in t cell aging and aging related dysfunction |
| topic | Immunosenescence T cell aging DNA methylation Immune aging T cell metabolism T cell dysfunction |
| url | https://doi.org/10.1186/s12929-025-01146-6 |
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