cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging
Aging is associated with an increased incidence of autoimmune diseases, despite the progressive decline of immune responses (immunosenescence). This apparent paradox can be explained by the age-related chronic low-grade systemic inflammation (inflammaging) and progressive dysregulation of innate sig...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1132653/full |
| _version_ | 1828003436642172928 |
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| author | Carine Raquel Richter Schmitz Carine Raquel Richter Schmitz Rafael Moura Maurmann Rafael Moura Maurmann Fatima T. C. R. Guma Moisés Evandro Bauer Moisés Evandro Bauer Moisés Evandro Bauer Moisés Evandro Bauer Florencia Maria Barbé-Tuana Florencia Maria Barbé-Tuana Florencia Maria Barbé-Tuana Florencia Maria Barbé-Tuana |
| author_facet | Carine Raquel Richter Schmitz Carine Raquel Richter Schmitz Rafael Moura Maurmann Rafael Moura Maurmann Fatima T. C. R. Guma Moisés Evandro Bauer Moisés Evandro Bauer Moisés Evandro Bauer Moisés Evandro Bauer Florencia Maria Barbé-Tuana Florencia Maria Barbé-Tuana Florencia Maria Barbé-Tuana Florencia Maria Barbé-Tuana |
| author_sort | Carine Raquel Richter Schmitz |
| collection | DOAJ |
| description | Aging is associated with an increased incidence of autoimmune diseases, despite the progressive decline of immune responses (immunosenescence). This apparent paradox can be explained by the age-related chronic low-grade systemic inflammation (inflammaging) and progressive dysregulation of innate signaling. During cellular aging, there is an accumulation of damaged DNA in the cell’s cytoplasm, which serves as ubiquitous danger-associated molecule, promptly recognized by DNA sensors. For instance, the free cytoplasmic DNA can be recognized, by DNA-sensing molecules like cGAS-STING (cyclic GMP-AMP synthase linked to a stimulator of interferon genes), triggering transcriptional factors involved in the secretion of pro-inflammatory mediators. However, the contribution of this pathway to the aging immune system remains largely unknown. Here, we highlight recent advances in understanding the biology of the cGAS-STING pathway, its influence on the senescence-associated secretory phenotype (SASP), and its modulation of the immune system during sterile inflammation. We propose that this important stress sensor of DNA damage is also a trigger of immunosenescence and inflammaging. |
| first_indexed | 2024-04-10T06:58:29Z |
| format | Article |
| id | doaj.art-afd6178a898243d6bedaae15a81ebd27 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T06:58:29Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-afd6178a898243d6bedaae15a81ebd272023-02-28T05:32:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11326531132653cGAS-STING pathway as a potential trigger of immunosenescence and inflammagingCarine Raquel Richter Schmitz0Carine Raquel Richter Schmitz1Rafael Moura Maurmann2Rafael Moura Maurmann3Fatima T. C. R. Guma4Moisés Evandro Bauer5Moisés Evandro Bauer6Moisés Evandro Bauer7Moisés Evandro Bauer8Florencia Maria Barbé-Tuana9Florencia Maria Barbé-Tuana10Florencia Maria Barbé-Tuana11Florencia Maria Barbé-Tuana12Laboratório de Imunobiologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilPrograma de Pós-Graduação em Ciência Biológicas - Bioquímica, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilLaboratório de Imunobiologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilPrograma de Pós-Graduação em Ciência Biológicas - Bioquímica, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilLaboratório de Imunobiologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilInstituto Nacional de Ciência e Tecnologia – Neuroimunomodulação (INCT-NIM), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brasília, BrazilPrograma de Pós-Graduação em Gerontologia Biomédica, Escola de Medicina, Pontifícia Universidade do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilLaboratório de Imunobiologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular da Escola de Ciências da Saúde da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, BrazilPrograma de Pós-Graduação em Pediatria e Saúde da Criança da Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, BrazilAging is associated with an increased incidence of autoimmune diseases, despite the progressive decline of immune responses (immunosenescence). This apparent paradox can be explained by the age-related chronic low-grade systemic inflammation (inflammaging) and progressive dysregulation of innate signaling. During cellular aging, there is an accumulation of damaged DNA in the cell’s cytoplasm, which serves as ubiquitous danger-associated molecule, promptly recognized by DNA sensors. For instance, the free cytoplasmic DNA can be recognized, by DNA-sensing molecules like cGAS-STING (cyclic GMP-AMP synthase linked to a stimulator of interferon genes), triggering transcriptional factors involved in the secretion of pro-inflammatory mediators. However, the contribution of this pathway to the aging immune system remains largely unknown. Here, we highlight recent advances in understanding the biology of the cGAS-STING pathway, its influence on the senescence-associated secretory phenotype (SASP), and its modulation of the immune system during sterile inflammation. We propose that this important stress sensor of DNA damage is also a trigger of immunosenescence and inflammaging. https://www.frontiersin.org/articles/10.3389/fimmu.2023.1132653/fullagingcGASimmunosenescenceinflammagingNF-κBSASP |
| spellingShingle | Carine Raquel Richter Schmitz Carine Raquel Richter Schmitz Rafael Moura Maurmann Rafael Moura Maurmann Fatima T. C. R. Guma Moisés Evandro Bauer Moisés Evandro Bauer Moisés Evandro Bauer Moisés Evandro Bauer Florencia Maria Barbé-Tuana Florencia Maria Barbé-Tuana Florencia Maria Barbé-Tuana Florencia Maria Barbé-Tuana cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging Frontiers in Immunology aging cGAS immunosenescence inflammaging NF-κB SASP |
| title | cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging |
| title_full | cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging |
| title_fullStr | cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging |
| title_full_unstemmed | cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging |
| title_short | cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging |
| title_sort | cgas sting pathway as a potential trigger of immunosenescence and inflammaging |
| topic | aging cGAS immunosenescence inflammaging NF-κB SASP |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1132653/full |
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