cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging

• Autor(a) principal: Schmitz, Carine Raquel Richter
• Data de Publicação: 2023
• Outros Autores: Maurmann, Rafael Moura, Guma, Fátima Theresinha Costa Rodrigues, Bauer, Moises Evandro, Tuana, Florencia María Barbé
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/256721
• topic: Senescência celular; Imunossenescência; Sistema imunitário; Aging; cGAS; Immunosenescence; Inflammaging; NF-kB; SASP; senescence

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.