Role of micronucleus-activated cGAS-STING signaling in antitumor immunity / 浙江大学学报·医学版

cGAS-STING signaling is a significant component of the innate immune system and functions as a vital sentinel mechanism to monitor cellular and tissue aberrations in microbial invasion and organ injury. cGAS, a cytosolic DNA sensor, is specialized in recognizing abnormally localized cytoplasmic double-stranded DNA (dsDNA) and catalytically synthesizes the second messenger cyclic-GMP-AMP (cGAMP), which initiates a cascade of type I interferon and inflammatory responses mediated by STING. Micronucleus, a byproduct of chromosomal missegregation during anaphase, are also significant contributors to cytoplasmic dsDNA. These unstable subcellular structures are susceptible to irreversible nuclear envelope rupture, exposing genomic dsDNA to the cytoplasm, which potently recruits cGAS and activates STING-mediated innate immune signaling and its downstream activities, including type I interferon and classical nuclear factor-κB (NF-κB) signaling pathways lead to senescence, apoptosis, autophagy activating anti-cancer immunity or directly killing tumor cells. However, sustained STING activation-induced endoplasmic reticulum stress, activated chronic type I interferon and nonclassical NF-κB signaling pathways remodel immunosuppressive tumor microenvironment, leading to immune evasion and facilitating tumor metastasis. Therefore, activated cGAS-STING signaling plays a dual role of suppressing or facilitating tumor growth in tumorigenesis and therapy. This review elaborates on research advances in mechanisms of micronucleus inducing activation of cGAS-STING signaling and its implications in tumorigenesis and therapeutic strategies of malignant tumors.

Mechanism of cGAS/STING Signaling Pathway in Regulating Lung Cancer and Traditional Chinese Medicine Treatment： A Review / 中国实验方剂学杂志

According to the latest global cancer statistics， the incidence and mortality of lung cancer rank first in China. Classical therapies remain the most common cancer treatment options， such as surgical resection， radiotherapy， and chemotherapy， but not all cancer patients respond to classical therapies， which require new lung cancer treatment strategies. After decades of research and development， cancer immunotherapy has achieved certain curative effect， which provides new possibilities for cancer treatment. Cyclic guanosine monophosphate-adenosine monophosphate synthase （cGAS） is a cytosolic DNA sensor. It can induce protective immune defense responses against various DNA-containing pathogens and provide anti-tumor immunity by activating the interferon （IFN） gene stimulator （STING） protein. At present， relevant researchers in China and abroad have done a lot of research on the occurrence and development of lung cancer and the pathophysiological mechanism of drug intervention in the treatment of lung cancer. The results show that cGAS/STING signaling pathway plays an important role in the development of the disease， and traditional Chinese medicine monomers or compounds can intervene in lung cancer cells by regulating the cGAS/STING signaling pathway， induce their autophagy and death， regulate their cycle operation， promote senescence， inhibit their proliferation and tumor angiogenesis， promote their invasion and metastasis， and promote the immune activation of anti-lung cancer cells， so as to inhibit or delay the occurrence and development of lung cancer. In recent years， the related research results have been updated rapidly， and the previous literature has not included the latest research results in time， which causes a lot of inconvenience for many scholars to search the literature. Based on this， this paper mainly summarized the mechanism of cGAS/STING signaling pathway intervention in lung cancer in China and abroad in recent years， as well as the research progress of related traditional Chinese medicine intervention， so as to provide new ideas for the development of lung cancer in molecular biology， drug treatment research， and clinical new drug research and provide a reference for further mechanism research.

Evaluation of anti-tumor effect of a novel manganese adjuvant collaborated with tumor antigens / 中国生物制品学杂志

@#ObjectiveTo investigate the anti-tumor effect of agonist MnCl_2of a novel cyclic guanosine monophosphate-adenosine monophosphate synthase(c GAS)/stimulator of interferon genes(STING)pathway collaborated with tumor cell lysate(Lysate)and the neo-antigen 10K-Adpgk of mouse colon cancer MC38 cell line.MethodsBone marrow-derived dendritic cells(BMDCs)were extracted from mouse bone marrow and divided into three groups:PBS,1 μmol/L MnCl_2and 10 μmol/L MnCl_2,which were analyzed for the maturation by flow cytometry,determined for the concentration of IL-6 in supernatant by ELISA,and detected for the transcription levels of IL-6,IFN-α,IFN β and CXCL9 genes by q PCR.Mouse tumor model was established by using MC38 cell line.When the tumor volume reached 100 mm3,the mice were randomly divided into two groups for administration,PBS,Lysate,MnCl_2,10K-Adpgk,Lysate + MnCl_2group and Lysate +10K-Adpgk + MnCl_2combined treatment group,which were administered subcutaneously through the tail for 3 times,with each interval of 1 week,and measured for the tumor volume every 2 days.One week after the last dose,serum samples were collected and determined for the concentrations of IFNγ and TNFα by ELISA.The tumor and spleen were isolated.The proportions of tumor infiltrating T cells and T cells in peripheral blood mononuclear cells(PBMCs)and the ratio of T cells to memory T cells in spleen were detected by flow cytometry,and the proportion of antigen specific T cells in spleen was detected by ELISPOT.Results10 μmol/L MnCl_2stimulated the maturation of BMDCs and activated the subsequent immune process.The tumor volumes of mice in the combined treatment group were considerably smaller than those in PBS group,the contents of IFNγ and TNF-α in serum were higher than those in other groups,and the proportions of tumor infiltrating T cells,T cells in PBMCs and ratio of T cells to memory T cells in spleen were also significantly higher than those in PBS group.Combined therapy caused strong antigen-specific T cell immune response.ConclusionThe addition of the novel adjuvant MnCl_2significantly enhanced the treatment effect of tumor cell lysate and neo-antigen,which provided an experimental basis for the development of the combination tumor treatment method based on MnCl_2and tumor antigens.

Progress in DNA-sensing pathways in Epstein-Barr virus infection / 中华微生物学和免疫学杂志

Epstein-Barr virus (EBV) is generally susceptible in human beings and multi-organ systems can be involved in EBV infection, such as blood, respiratory, urinary, digestive and nervous systems. EBV infection also plays an important role in the pathogenesis of related tumors, autoimmune diseases and other diseases, posing a great threat to human health. As a DNA virus, EBV can be sensed by DNA recognition receptors to trigger a series of downstream immune responses. A DNA-sensing pathway consists of DNA sensors, adaptor molecules and downstream effector signals. Double-stranded DNA sensors mainly include absent in melanoma 2-like receptors (ALRs) and cyclic GMP-AMP synthase (cGAS). Adaptors were mainly stimulator of interferon genes (STING) and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Downstream immune responses mainly involve typeⅠIFN, inflammasomes and proinflammatory cytokines. As a double-stranded DNA virus of the Herpesviridae family, EBV triggers complex innate and adaptive immune responses in the host, especially the sensing pathways mediated by a variety of DNA recognition receptors, which play a key role in host immune defense and pathogen immune evasion. This review made the DNA sensor as the clue to comprehensively summarize the progress in the activation, regulatory mechanism and clinical relevance of DNA-sensing pathways in EBV infection in recent years, aiming to achieve a better understanding of the host innate immune responses during EBV infection and provide an immunological basis for the prevention and treatment of EBV infection-related diseases.

Recent progress on cGAS-STING pathway in tumor radiotherapy / 中华放射肿瘤学杂志

Radiotherapy is widely used in the treatment of primary and metastatic malignant tumors. It is traditionally believed that the killing effect of radiotherapy on tumor is based on the direct or indirect damage of ionizing radiation to DNA. In recent years, the anti-tumor role and mechanism of anti-tumor immune response induced by ionizing radiation have captivated widespread attention and achieved significant progress. Among them, Cyclic GMP-AMP synthase (cGAS)-stimulator of interference genes (STING) pathway is considered to be one of the key regulatory hubs. cGAS is a cytoplasmic DNA receptor that can bind to tumor-derived double-stranded DNA and activate the downstream STING, thereby activating anti-tumor immune response of the host. In view of the latest progress in this field, the important role and potential mechanism of cGAS-STING pathway in radiotherapy immune effect were mainly summarized, and the application prospect of targeting cGAS-STING pathway in radiotherapy sensitization was explored.

Tetrahydroxy stilbene glycoside ameliorates neuroin-flammation for Alzheimer's disease via cGAS-STING / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.

Phase separation in cGAS-STING signaling / 医学前沿

Biomolecular condensates formed by phase separation are widespread and play critical roles in many physiological and pathological processes. cGAS-STING signaling functions to detect aberrant DNA signals to initiate anti-infection defense and antitumor immunity. At the same time, cGAS-STING signaling must be carefully regulated to maintain immune homeostasis. Interestingly, exciting recent studies have reported that biomolecular phase separation exists and plays important roles in different steps of cGAS-STING signaling, including cGAS condensates, STING condensates, and IRF3 condensates. In addition, several intracellular and extracellular factors have been proposed to modulate the condensates in cGAS-STING signaling. These studies reveal novel activation and regulation mechanisms of cGAS-STING signaling and provide new opportunities for drug discovery. Here, we summarize recent advances in the phase separation of cGAS-STING signaling and the development of potential drugs targeting these innate immune condensates.

The I226R protein of African swine fever virus inhibits the cGAS-STING-mediated innate immune response / 生物工程学报

This study aimed to explore the mechanism of how African swine fever virus (ASFV) I226R protein inhibits the cGAS-STING signaling pathway. We observed that I226R protein (pI226R) significantly inhibited the cGAS-STING-mediated type Ⅰ interferons and the interferon-stimulated genes production by dual-luciferase reporter assay system and real-time quantitative PCR. The results of co-immunoprecipitation assay and confocal microscopy showed that pI226R interacted with cGAS. Furthermore, pI226R promoted cGAS degradation through autophagy-lysosome pathway. Moreover, we found that pI226R decreased the binding of cGAS to E3 ligase tripartite motif protein 56 (TRIM56), resulting in the weakened monoubiquitination of cGAS, thus inhibiting the activation of cGAS and cGAS-STING signaling. In conclusion, ASFV pI226R suppresses the antiviral innate immune response by antagonizing cGAS, which contributes to an in-depth understanding of the immune escape mechanism of ASFV and provides a theoretical basis for the development of vaccines.

Prospective insight into the role of benzyl propylene glycoside as a modulator of the cGAS-STING signaling pathway in the management of nonalcoholic fatty pancreas animal model

BACKGROUND: Nonalcoholic fatty pancreatitis (NAFP) is one of the metabolic syndrome manifestations that need further studies to determine its molecular determinants and find effective medications. We aimed to investigate the potential effect of benzyl propylene glycoside on NAFP management via targeting the pancreatic cGAS-STING pathway-related genes (DDX58, NFκB1 & CHUK) and their upstream regulator miRNA (miR-1976) that were retrieved from bioinformatics analysis. METHODS: The rats were fed either normal chow or a high-fat high-sucrose diet (HFHS), as a nutritional model for NAFP. After 8 weeks, the HFHS-fed rats were subdivided randomly into 4 groups; untreated HFHS group (NAFP model group) and three treated groups which received 3 doses of benzyl propylene glycoside (10, 20, and 30 mg/kg) daily for 4 weeks, parallel with HFHS feeding. RESULTS: The molecular analysis revealed that benzyl propylene glycoside could modulate the expression of the pancreatic cGAS-STING pathway-related through the downregulation of the expression of DDX58, NFκB1, and CHUK mRNAs and upregulation of miR-1976 expression. Moreover, the applied treatment reversed insulin resistance, inflammation, and fibrosis observed in the untreated NAFP group, as evidenced by improved lipid panel, decreased body weight and the serum level of lipase and amylase, reduced protein levels of NFκB1 and caspase-3 with a significant reduction in area % of collagen fibers in the pancreatic sections of treated animals. CONCLUSION: benzyl propylene glycoside showed a potential ability to attenuate NAFP development, inhibit pancreatic inflammation and fibrosis and reduce the pathological and metabolic disturbances monitored in the applied NAFP animal model. The detected effect was correlated with modulation of the expression of pancreatic (DDX58, NFκB1, and CHUK mRNAs and miR-1976) panel.

Research progress of novel drug delivery system for STING agonist / 中国药理学通报

Stimulator of interferon genes(STING)is a key protein in cGAS-STING signaling pathway and plays an important role in immune response mediated by the exogenous or endogenous DNA.This review describes the biological function of STING, the process of cGAS-STING pathway, the classification and administration of STING agonists, and summarizes the currently reported drug delivery systems.The delivery of STING agonists through appropriate drug carriers can overcome the lack of difficult entry, easy enzymatic hydrolysis, short half-life and poor targeting, improve the body's innate and adaptive immunity, and enhance the therapeutic effect of drugs.In conclusion, this paper mainly reviews the research progress of drug delivery system for STING agonists to provide basis for the development of drug delivery system and promote the clinical transformation and application of STING agonists.

DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis

Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan (CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA (dsDNA) from the intestine, leading to cyclic-GMP-AMP synthase (cGAS)‒stimulator of interferon genes (STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination (HR) repair and downregulate dsDNA‒cGAS‒STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.

Nuclear cGAS: sequestration and beyond

The cyclic GMP-AMP (cGAMP) synthase (cGAS) has been identified as a cytosolic double stranded DNA sensor that plays a pivotal role in the type I interferon and inflammation responses via the STING-dependent signaling pathway. In the past several years, a growing body of evidence has revealed that cGAS is also localized in the nucleus where it is associated with distinct nuclear substructures such as nucleosomes, DNA replication forks, the double-stranded breaks, and centromeres, suggesting that cGAS may have other functions in addition to its role in DNA sensing. However, while the innate immune function of cGAS is well established, the non-canonical nuclear function of cGAS remains poorly understood. Here, we review our current understanding of the complex nature of nuclear cGAS and point to open questions on the novel roles and the mechanisms of action of this protein as a key regulator of cell nuclear function, beyond its well-established role in dsDNA sensing and innate immune response.

The E248R protein of African swine fever virus inhibits the cGAS-STING-mediated innate immunity / 生物工程学报

We researched the mechanism of African swine fever virus (ASFV) protein E248R in regulating the cGAS-STING pathway. First, we verified via the dual-luciferase reporter assay system that E248R protein inhibited the secretion of IFN-β induced by cGAS-STING or HT-DNA in a dose-dependent manner. The relative quantitative PCR analysis indicated that the overexpression of E248R inhibited HT-DNA-induced transcription of IFN-b1, RANTES, IL-6, and TNF-α in PK-15 cells. Next, we found that E248R interacted with STING by co-immunoprecipitation assay and laser confocal microscopy. Finally, we demonstrated that E248R inhibited the expression of STING protein by using Western blotting. We demonstrated for the first time that the E248R protein of ASFV suppressed the host innate immune response via inhibiting STING expression. The results are pivotal in extending the understanding of the ASFV immune escape and can guide the design of vaccines against ASFV.

Palmitic acid suppresses autophagy in neonatal rat cardiomyocytes via the cGAS-STING-IRF3 pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of palmitic acid (PA) on autophagy in neonatal rat cardiomyocytes (NRCMs) and explore the underlying mechanism.@*METHODS@#NRCMs were isolated and cultured for 24 h before exposure to 10% BSA and 0.1, 0.3, 0.5, or 0.7 mmol/L PA for 24 h. After the treatments, the expressions of Parkin, PINK1, p62, LC3Ⅱ/ LC3Ⅰ, cGAS, STING and p-IRF3/IRF3 were detected using Western blotting and the cell viability was assessed with CCK8 assay, based on which 0.7 mmol/L was selected as the optimal concentration in subsequent experiments. The effects of cGAS knockdown mediated by cGAS siRNA in the presence of PA on autophagy-related proteins in the NRCMs were determined using Western blotting, and the expressions of P62 and LC3 in the treated cells were examined using immunofluorescence assay.@*RESULTS@#PA at different concentrations significantly lowered the expressions of Parkin, PINK1, LC3 Ⅱ/LC3 Ⅰ and LC3 Ⅱ/LC3 Ⅰ+Ⅱ (P < 0.05), increased the expression of p62 (P < 0.05), and inhibited the viability of NRCMs (P < 0.05). Knockdown of cGAS obviously blocked the autophagy-suppressing effect of PA and improved the viability of NRCMs (P < 0.05).@*CONCLUSION@#PA inhibits autophagy by activating the cGAS-STING-IRF3 pathway to reduce the viability of NRCMs.

cGAS guards against chromosome end-to-end fusions during mitosis and facilitates replicative senescence

As a sensor of cytosolic DNA, the role of cyclic GMP-AMP synthase (cGAS) in innate immune response is well established, yet how its functions in different biological conditions remain to be elucidated. Here, we identify cGAS as an essential regulator in inhibiting mitotic DNA double-strand break (DSB) repair and protecting short telomeres from end-to-end fusion independent of the canonical cGAS-STING pathway. cGAS associates with telomeric/subtelomeric DNA during mitosis when TRF1/TRF2/POT1 are deficient on telomeres. Depletion of cGAS leads to mitotic chromosome end-to-end fusions predominantly occurring between short telomeres. Mechanistically, cGAS interacts with CDK1 and positions them to chromosome ends. Thus, CDK1 inhibits mitotic non-homologous end joining (NHEJ) by blocking the recruitment of RNF8. cGAS-deficient human primary cells are defective in entering replicative senescence and display chromosome end-to-end fusions, genome instability and prolonged growth arrest. Altogether, cGAS safeguards genome stability by controlling mitotic DSB repair to inhibit mitotic chromosome end-to-end fusions, thus facilitating replicative senescence.

Intravitreal injection of mitochondrial DNA induces cell damage and retinal dysfunction in rats

BACKGROUND: Retinal neurodegeneration is induced by a variety of environmental insults and stresses, but the exact mechanisms are unclear. In the present study, we explored the involvement of cytosolic mitochondrial DNA (mtDNA), resulting in the cGAS-STING dependent inflammatory response and apoptosis in retinal damage in vivo. METHODS: Retinal injury was induced with white light or intravitreal injection of lipopolysaccharide (LPS). After light-or LPS-induced injury, the amount of cytosolic mtDNA in the retina was detected by PCR. The mtDNA was isolated and used to transfect retinas in vivo. WB and real-time PCR were used to evaluate the activation of cGAS-STING path-way and the levels of apoptosis-associated protein at different times after mtDNA injection. Retinal cell apoptosis rate was detected by TUNEL staining. Full-field electroretinography (ERG) was used to assess the retinal function. RESULTS: Light injury and the intravitreal injection of LPS both caused the leakage of mtDNA into the cytoplasm in retinal tissue. After the transfection of mtDNA in vivo, the levels of cGAS, STING, and IFN-ß mRNAs and the protein levels of STING, phosph-TBK1, phospho-IRF3, and IFN-ß were upregulated. mtDNA injection also induced the activation of caspase 3 and caspase 9. BAX and BAK were increased at both the mRNA and protein levels. The release of cytochrome c from the mitochondria to the cytosol was increased after mtDNA injection. The wave amplitudes on ERG decreased and retinal cell apoptosis was detected after mtDNA injection. CONCLUSIONS: Cytosolic mtDNA triggers an inflammatory response. It also promotes apoptosis and the dysfunction of the retina.

Higher-order assemblies in immune signaling: supramolecular complexes and phase separation

Signaling pathways in innate and adaptive immunity play vital roles in pathogen recognition and the functions of immune cells. Higher-order assemblies have recently emerged as a central principle that governs immune signaling and, by extension, cellular communication in general. There are mainly two types of higher-order assemblies: 1) ordered, solid-like large supramolecular complexes formed by stable and rigid protein-protein interactions, and 2) liquid-like phase-separated condensates formed by weaker and more dynamic intermolecular interactions. This review covers key examples of both types of higher-order assemblies in major immune pathways. By placing emphasis on the molecular structures of the examples provided, we discuss how their structural organization enables elegant mechanisms of signaling regulation.

Role of cGAS-cGAMP-STING pathway in antivirus / 药学实践杂志

Innate immunity is the host's first line defense against pathogens invading to the body. Detection of abnormal nucleic acids in the cytoplasm showed that some conserved pathogen associated molecular patterns (PAMPS) triggered type I interferon (IFN) -mediated innate immune responses. The DNA sensor— cGAS (cGAMP Synthase) recognizes and binds to host or pathogen cytoplasmic DNA, promotes the formation of the second messenger cGAMP (cyclic GMP-AMP), and triggers STING (stimulator of interferon genes) dependent downstream signaling. Here we briefly describe the latest progress of the cGAS-cGAMP-STING pathway and its important role in antivirus, and provide new ideas for virus prevention research and new direction for the development of antiviral drugs.

Research advances on stimulator of interferon genes (STING) and its agonists / 药学学报

As a key signal transduction molecule involved in the innate immune response, stimulator of interferon genes (STING) is triggered by cytosolic DNA from pathogen and host origins, and plays an important role in inducing the secretion of type I interferons and proinflammatory cytokines, thereby defending against viral and intracellular bacterial infections and regulating the production of spontaneous antitumor immune responses in vivo. Thus, STING agonists have shown useful therapeutic effects for pathogen infection and cancer. In the past decade research on STING and its agonists has progressed rapidly. Here, we summarize recent advances in the structure and activation of STING and the mechanism of the cGAS-STING pathway. In particular, we review research advances of STING agonists, analyze the crystal structure of STING in complex with its agonists and the structure-activity relationship of STING agonists, and summarize the strong challenges of developing STING agonists.

Senile disease regulates aging-related secretion phenotype through cGAS-STING pathway / 中国药理学通报

Aging is one of the most important risk factors for human diseases such as cancer, cardiovascular diseases, diabetes and neurodegenerative diseases, and many aging diseases are related to cellular aging. Cells show profound phenotypic changes during aging, which are driven by changes in metabolism, chromatin organizationand transcriptional activity. A significant feature of aging is the secretion of inflammatory mediators, including various cytokines, chemokines, extracellular matrix proteins and growth factors, collectively known as the aging-related secreted phenotype (SASP). By secreting SASP, senescent cells have important effects on many biological processes, such as wound healing, tissue repair, tumor formation, or in vivo reorganization. In addition, the inflammatory response associated with SASP is considered to be the basis of aging-related diseases, and the discovery of new targets to control the response of aging effects is crucial. Recent scientific advances have shown that innate immune responses, particularly those involving the cGAS-STING pathway, trigger SASP. In this article, we review the biological function and regulatory mechanism of SASP through the cGAS-STING signaling pathway in aging diseases.