Nuclear Sirtuins and the Aging of the Immune System
The immune system undergoes major changes with age that result in altered immune populations, persistent inflammation, and a reduced ability to mount effective immune responses against pathogens and cancer cells. Aging-associated changes in the immune system are connected to other age-related diseas...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/12/1856 |
| _version_ | 1797504326035308544 |
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| author | Andrés Gámez-García Berta N. Vazquez |
| author_facet | Andrés Gámez-García Berta N. Vazquez |
| author_sort | Andrés Gámez-García |
| collection | DOAJ |
| description | The immune system undergoes major changes with age that result in altered immune populations, persistent inflammation, and a reduced ability to mount effective immune responses against pathogens and cancer cells. Aging-associated changes in the immune system are connected to other age-related diseases, suggesting that immune system rejuvenation may provide a feasible route to improving overall health in the elderly. The Sir2 family of proteins, also called sirtuins, have been broadly implicated in genome homeostasis, cellular metabolism, and aging. Sirtuins are key responders to cellular and environmental stress and, in the case of the nuclear sirtuins, they do so by directing responses to chromatin that include gene expression regulation, retrotransposon repression, enhanced DNA damage repair, and faithful chromosome segregation. In the immune system, sirtuins instruct cellular differentiation from hematopoietic precursors and promote leukocyte polarization and activation. In hematopoietic stem cells, sirtuins safeguard quiescence and stemness to prevent cellular exhaustion. Regulation of cytokine production, which, in many cases, requires NF-κB regulation, is the best-characterized mechanism by which sirtuins control innate immune reactivity. In adaptive immunity, sirtuins promote T cell subset differentiation by controlling master regulators, thereby ensuring an optimal balance of helper (Th) T cell-dependent responses. Sirtuins are very important for immune regulation, but the means by which they regulate immunosenescence are not well understood. This review provides an integrative overview of the changes associated with immune system aging and its potential relationship with the roles of nuclear sirtuins in immune cells and overall organismal aging. Given the anti-aging properties of sirtuins, understanding how they contribute to immune responses is of vital importance and may help us develop novel strategies to improve immune performance in the aging organism. |
| first_indexed | 2024-03-10T04:03:02Z |
| format | Article |
| id | doaj.art-17db615c247a4390a8c093c0a625e795 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T04:03:02Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-17db615c247a4390a8c093c0a625e7952023-11-23T08:29:27ZengMDPI AGGenes2073-44252021-11-011212185610.3390/genes12121856Nuclear Sirtuins and the Aging of the Immune SystemAndrés Gámez-García0Berta N. Vazquez1Chromatin Biology Laboratory, Josep Carreras Leukaemia Research Institute (IJC), Ctra de Can Ruti, Camí de les Escoles s/n, 08916 Badalona, SpainChromatin Biology Laboratory, Josep Carreras Leukaemia Research Institute (IJC), Ctra de Can Ruti, Camí de les Escoles s/n, 08916 Badalona, SpainThe immune system undergoes major changes with age that result in altered immune populations, persistent inflammation, and a reduced ability to mount effective immune responses against pathogens and cancer cells. Aging-associated changes in the immune system are connected to other age-related diseases, suggesting that immune system rejuvenation may provide a feasible route to improving overall health in the elderly. The Sir2 family of proteins, also called sirtuins, have been broadly implicated in genome homeostasis, cellular metabolism, and aging. Sirtuins are key responders to cellular and environmental stress and, in the case of the nuclear sirtuins, they do so by directing responses to chromatin that include gene expression regulation, retrotransposon repression, enhanced DNA damage repair, and faithful chromosome segregation. In the immune system, sirtuins instruct cellular differentiation from hematopoietic precursors and promote leukocyte polarization and activation. In hematopoietic stem cells, sirtuins safeguard quiescence and stemness to prevent cellular exhaustion. Regulation of cytokine production, which, in many cases, requires NF-κB regulation, is the best-characterized mechanism by which sirtuins control innate immune reactivity. In adaptive immunity, sirtuins promote T cell subset differentiation by controlling master regulators, thereby ensuring an optimal balance of helper (Th) T cell-dependent responses. Sirtuins are very important for immune regulation, but the means by which they regulate immunosenescence are not well understood. This review provides an integrative overview of the changes associated with immune system aging and its potential relationship with the roles of nuclear sirtuins in immune cells and overall organismal aging. Given the anti-aging properties of sirtuins, understanding how they contribute to immune responses is of vital importance and may help us develop novel strategies to improve immune performance in the aging organism.https://www.mdpi.com/2073-4425/12/12/1856sirtuinsepigeneticsagingimmune systemimmune senescenceinflammation |
| spellingShingle | Andrés Gámez-García Berta N. Vazquez Nuclear Sirtuins and the Aging of the Immune System Genes sirtuins epigenetics aging immune system immune senescence inflammation |
| title | Nuclear Sirtuins and the Aging of the Immune System |
| title_full | Nuclear Sirtuins and the Aging of the Immune System |
| title_fullStr | Nuclear Sirtuins and the Aging of the Immune System |
| title_full_unstemmed | Nuclear Sirtuins and the Aging of the Immune System |
| title_short | Nuclear Sirtuins and the Aging of the Immune System |
| title_sort | nuclear sirtuins and the aging of the immune system |
| topic | sirtuins epigenetics aging immune system immune senescence inflammation |
| url | https://www.mdpi.com/2073-4425/12/12/1856 |
| work_keys_str_mv | AT andresgamezgarcia nuclearsirtuinsandtheagingoftheimmunesystem AT bertanvazquez nuclearsirtuinsandtheagingoftheimmunesystem |