cGAS-STING pathway drives cellular senescence and inflammaging

Abstract

Cellular senescence is a cell fate triggered by diverse endogenous and exogenous stresses, including DNA damage, telomere dysfunction, and metabolic dysregulation. It is characterized by irreversible cell cycle arrest and a hypersecretory state known as the senescence-associated secretory phenotype (SASP). As a hallmark of ageing, senescence contributes to various physiological processes and is closely associated with the pathogenesis of age-related diseases. Specifically, senescent cells secrete SASP factors, which promote chronic inflammation, and propagate senescence to neighboring normal cells. DNA damage, a crucial inducer of cellular senescence and inflammation, often leads to the accumulation of cytosolic DNA. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway has emerged as a critical mechanism for detecting such intracellular DNA, and its excessive activation is strongly associated with senescence and age-related chronic inflammation (inflammaging). Accumulating evidence indicates that multiple factors can trigger cGAS-STING signaling, thereby stimulating inflammatory responses and accelerating cellular senescence. In this review, we summarize recent advances in understanding how cGAS-STING signaling orchestrates cellular senescence and inflammaging. We outline the key hallmarks and triggers of cellular senescence, with particular emphasis on the role of cGAS in age-related inflammatory diseases. Finally, we discuss that targeting the cGAS-STING pathway may pave new ways for therapeutic strategies to mitigate cellular senescence-associated diseases.

Keywords

Cellular senescence / inflammaging / cGAS / STING / DNA damage

1 Authors contribution

Chen Y, Chen K: Conceptualization, writing-review & editing.

2 Conflict of interest

The authors declare that they have no conflict of interest.

3 Ethical approval

Not applicable.

4 Consent to participate

Not applicable.

5 Consent for publication

Not applicable.

6 Availability of data and materials

Not applicable.

Funding

This work was supported by the grants from the National Natural Science Foundation of China (Grant No. 32500791), the Fundamental Research Funds for the Central Universities (Grant Nos. 22120250158, 22120250374, and 22120260165).

References

[1] Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E.From discoveries in ageing research to therapeutics for healthy ageing. Nature. 2019; 571(7764):183-192.

[2] Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: A new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018; 14(10):576-590.

[3] Zhu X, Chen Z, Shen W, Huang G, Sedivy JM, Wang H, et al. Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: The regulation and intervention. Sig Transduct Target Ther. 2021; 6(1):245.

[4] Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, et al. Cellular senescence: Defining a path forward. Cell. 2019; 179(4):813-827.

[5] Di Micco R, Krizhanovsky V, Baker D, d’Adda di Fagagna F. Cellular senescence in ageing: From mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol. 2021; 22(2):75-95.

[6] Zhao Y, Simon M, Seluanov A, Gorbunova V. DNA damage and repair in age-related inflammation. Nat Rev Immunol. 2023; 23(2):75-89.

[7] Decout A, Katz JD, Venkatraman S, Ablasser A. The cGAS-STING pathway as a therapeutic target in inflammatory diseases. Nat Rev Immunol. 2021; 21(9):548-569.

[8] Ablasser A, Chen ZJ. cGAS in action: Expanding roles in immunity and inflammation. Science. 2019; 363(6431):eaat8657.

[9] Glück S, Guey B, Gulen MF, Wolter K, Kang TW, Schmacke NA, et al. Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence. Nat Cell Biol. 2017; 19(9):1061-1070.

[10] Motwani M, Pesiridis S, Fitzgerald KA. DNA sensing by the cGAS-STING pathway in health and disease. Nat Rev Genet. 2019; 20(11):657-674.

[11] Li T, Chen ZJ. The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer. J Exp Med. 2018; 215(5):1287-1299.

[12] Zhang B, Xu P, Ablasser A. Regulation of the cGAS-STING pathway. Annu Rev Immunol. 2025; 43:667-692.

[13] Dou Z, Ghosh K, Vizioli MG, Zhu J, Sen P, Wangensteen KJ, et al. Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature. 2017; 550(7676):402-406.

[14] Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of cellular senescence. Trends Cell Biol. 2018; 28(6):436-453.

[15] Ogrodnik M, Carlos Acosta J, Adams PD, d’Adda di Fagagna F, Baker DJ, Bishop CL, et al. Guidelines for minimal information on cellular senescence experimentation in vivo. Cell. 2024; 187(16):4150-4175.

[16] Richardson AG, Schadt EE. The role of macromolecular damage in aging and age-related disease. J Gerontol Ser A Biol Sci Med Sci. 2014; 69(Suppl 1):S28-S32.

[17] Höhn A, Weber D, Jung T, Ott C, Hugo M, Kochlik B, et al. Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence. Redox Biol. 2017; 11:482-501.

[18] Correia‐Melo C, Marques FD, Anderson R, Hewitt G, Hewitt R, Cole J, et al. Mitochondria are required for pro‐ageing features of the senescent phenotype. EMBO J. 2016; 35(7):724-742.

[19] Wiley CD, Velarde MC, Lecot P, Liu S, Sarnoski EA, Freund A, et al. Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab. 2016; 23(2):303-314.

[20] Park JT, Lee YS, Cho KA, Park SC. Adjustment of the lysosomal-mitochondrial axis for control of cellular senescence. Ageing Res Rev. 2018; 47:176-182.

[21] Abuetabh Y, Wu HH, Chai C, Al Yousef H, Persad S, Sergi CM, et al. DNA damage response revisited: The p53 family and its regulators provide endless cancer therapy opportunities. Exp Mol Med. 2022; 54(10):1658-1669.

[22] Shay JW, Wright WE. Telomeres and telomerase: Three decades of progress. Nat Rev Genet. 2019; 20(5):299-309.

[23] Chakravarti D, LaBella KA, DePinho RA. Telomeres: History, health, and hallmarks of aging. Cell. 2021; 184(2):306-322.

[24] Nguyen TT, Mazzucco G, Kyriacou E, Lunardi T, Brandl L, Ahmed W, et al. Oxidative stress at telomeres triggers internal DNA loops, TRF 1 dissociation, and TRF2-dependent R-loops. Nucleic Acids Res. 2025; 53(7):gkaf285.

[25] De Rosa M, Barnes RP, Detwiler AC, Nyalapatla PR, Wipf P, Opresko PL. OGG1 and MUTYH repair activities promote telomeric 8-oxoguanine induced senescence in human fibroblasts. Nat Commun. 2025; 16:893.

[26] Rossiello F, Jurk D, Passos JF, d’Adda di Fagagna F. Telomere dysfunction in ageing and age-related diseases. Nat Cell Biol. 2022; 24(2):135-147.

[27] Bloom SI, Liu Y, Tucker JR, Islam MT, Machin DR, Abdeahad H, et al. Endothelial cell telomere dysfunction induces senescence and results in vascular and metabolic impairments. Aging Cell. 2023; 22(8):e13875.

[28] Vodicka P, Vodenkova S, Danesova N, Vodickova L, Zobalova R, Tomasova K, et al. Mitochondrial DNA damage, repair, and replacement in cancer. Trends Cancer. 2025; 11(1):62-73.

[29] Xian H, Watari K, Sanchez-Lopez E, Offenberger J, Onyuru J, Sampath H, et al. Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP 3 inflammasome and interferon signaling. Immunity. 2022; 55(8):1370-1385.e8.

[30] Hahn A, Hung GCC, Ahier A, Dai CY, Kirmes I, Forde BM, et al. Misregulation of mitochondrial 6mA promotes the propagation of mutant mtDNA and causes aging in C. elegans. Cell Metab. 2024; 36(12):2528-2541.e11.

[31] Sun N, Youle RJ, Finkel T. The mitochondrial basis of aging. Mol Cell. 2016; 61(5):654-666.

[32] Victorelli S, Salmonowicz H, Chapman J, Martini H, Vizioli MG, Riley JS, et al. Apoptotic stress causes mtDNA release during senescence and drives the SASP. Nature. 2023; 622(7983):627-636.

[33] Vargas JNS, Hamasaki M, Kawabata T, Youle RJ, Yoshimori T. The mechanisms and roles of selective autophagy in mammals. Nat Rev Mol Cell Biol. 2023; 24(3):167-185.

[34] García-Prat L, Martínez-Vicente M, Perdiguero E, Ortet L, Rodríguez-Ubreva J, Rebollo E, et al. Autophagy maintains stemness by preventing senescence. Nature. 2016; 529(7584):37-42.

[35] Wu Z, Qu J, Liu GH. Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases. Nat Rev Mol Cell Biol. 2024; 25(12):979-1000.

[36] Lee JH, Kim EW, Croteau DL, Bohr VA. Heterochromatin: An epigenetic point of view in aging. Exp Mol Med. 2020; 52(9):1466-1474.

[37] Lee JH, Demarest TG, Babbar M, Kim EW, Okur MN, De S, et al. Cockayne syndrome group B deficiency reduces H3K9me3 chromatin remodeler SETDB1 and exacerbates cellular aging. Nucleic Acids Res. 2019; 47(16):8548-8562.

[38] Deng P, Yuan Q, Cheng Y, Li J, Liu Z, Liu Y, et al. Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging. Cell Stem Cell. 2021; 28(6):1057-1073.e7.

[39] Zhu H, Blake S, Kusuma FK, Pearson RB, Kang J, Chan KT. Oncogene-induced senescence: From biology to therapy. Mech Ageing Dev. 2020; 187:111229.

[40] Suram A, Kaplunov J, Patel PL, Ruan H, Cerutti A, Boccardi V, et al. Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions. EMBO J. 2012; 31(13):2839-2851.

[41] Wu J, Sun L, Chen X, Du F, Shi H, Chen C, et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 2013; 339(6121):826-830.

[42] Zhang Z, Zhang C. Regulation of cGAS-STING signalling and its diversity of cellular outcomes. Nat Rev Immunol. 2025; 25(6):425-444.

[43] Jiménez-Loygorri JI, Villarejo-Zori B, Viedma-Poyatos Á, Zapata-Muñoz J, Benítez-Fernández R, Frutos-Lisón MD, et al. Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging. Nat Commun. 2024; 15(1):830.

[44] Dunphy G, Flannery SM, Almine JF, Connolly DJ, Paulus C, Jønsson KL, et al. Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signaling after nuclear DNA damage. Mol Cell. 2018; 71(5):745-760.e5.

[45] Zhang D, Liu Y, Zhu Y, Zhang Q, Guan H, Liu S, et al. A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis. Nat Cell Biol. 2022; 24(5):766-782.

[46] Chen Y, Chen Z, Wang H, Cui Z, Li KL, Song Z, et al. A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging. Science. 2025; 390(6769):eadp5056.

[47] Raab M, Gentili M, de Belly H, Thiam HR, Vargas P, Jimenez AJ, et al. ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death. Science. 2016; 352(6283):359-362.

[48] MacKenzie KJ, Carroll P, Martin CA, Murina O, Fluteau A, Simpson DJ, et al. cGAS surveillance of micronuclei links genome instability to innate immunity. Nature. 2017; 548(7668):461-465.

[49] Harding SM, Benci JL, Irianto J, Discher DE, Minn AJ, Greenberg RA. Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature. 2017; 548(7668):466-470.

[50] Sladitschek-Martens HL, Guarnieri A, Brumana G, Zanconato F, Battilana G, Xiccato RL, et al. YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS-STING. Nature. 2022; 607(7920):790-798.

[51] Chen Y, Wang L, Jin J, Luan Y, Chen C, Li Y, et al. p38 inhibition provides anti-DNA virus immunity by regulation of USP21 phosphorylation and STING activation. J Exp Med. 2017; 214(4):991-1010.

[52] Hopfner KP, Hornung V. Molecular mechanisms and cellular functions of cGAS-STING signalling. Nat Rev Mol Cell Biol. 2020; 21(9):501-521.

[53] de Oliveira Mann CC, Orzalli MH, King DS, Kagan JC, Lee ASY, Kranzusch PJ.Modular architecture of the STING C-terminal tail allows interferon and NF-κB signaling adaptation. Cell Rep. 2019; 27(4):1165-1175.e5.

[54] Konno H, Konno K, Barber GN. Cyclic dinucleotides trigger ULK 1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling. Cell. 2013; 155(3):688-698.

[55] Balka KR, Louis C, Saunders TL, Smith AM, Calleja DJ, D’Silva DB, et al.TBK1 and IKKε act redundantly to mediate STING-induced NF-κB responses in myeloid cells. Cell Rep. 2020; 31(1):107492.

[56] Yang H, Wang H, Ren J, Chen Q, Chen ZJ. cGAS is essential for cellular senescence. Proc Natl Acad Sci U S A. 2017; 114(23):E4612-E4620.

[57] West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature. 2015; 520(7548):553-557.

[58] Gulen MF, Samson N, Keller A, Schwabenland M, Liu C, Glück S, et al. cGAS-STING drives ageing-related inflammation and neurodegeneration. Nature. 2023; 620(7973):374-380.

[59] Bahat A, Milenkovic D, Cors E, Barnett M, Niftullayev S, Katsalifis A, et al. Ribonucleotide incorporation into mitochondrial DNA drives inflammation. Nature. 2025; 647(8090):726-734.

[60] Lai P, Liu L, Bancaro N, Troiani M, Calì B, Li Y, et al. Mitochondrial DNA released by senescent tumor cells enhances PMN-MDSC-driven immunosuppression through the cGAS-STING pathway. Immunity. 2025; 58(4):811-825.e7.

[61] Kim J, Gupta R, Blanco LP, Yang S, Shteinfer-Kuzmine A, Wang K, et al. VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease. Science. 2019; 366(6472):1531-1536.

[62] Li HY, Wei TT, Zhuang M, Tan CY, Xie TH, Cai J, et al. Iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway. Cell Death Discov. 2023; 9(1):419.

[63] Picca A, Faitg J, Auwerx J, Ferrucci L, D’Amico D. Mitophagy in human health, ageing and disease. Nat Metab. 2023; 5(12):2047-2061.

[64] Li J, Yang D, Li Z, Zhao M, Wang D, Sun Z, et al. PINK1/Parkin-mediated mitophagy in neurodegenerative diseases. Ageing Res Rev. 2023; 84:101817.

[65] Mohanty S, Suklabaidya S, Mnatsakanyan N, Jacobson S, Harhaj EW. HTLV-1 Tax induces PINK1-Parkin-dependent mitophagy to mitigate activation of the cGAS-STING pathway. bioRxiv [Preprint]. 2025.

[66] Miwa S, Kashyap S, Chini E, von Zglinicki T. Mitochondrial dysfunction in cell senescence and aging. J Clin Investig. 2022; 132(13):e158447.

[67] Martini H, Passos JF. Cellular senescence: All roads lead to mitochondria. FEBS J. 2023; 290(5):1186-1202.

[68] Luo W, Zou X, Wang Y, Dong Z, Weng X, Pei Z, et al. Critical role of the cGAS-STING pathway in doxorubicin-induced cardiotoxicity. Circ Res. 2023; 132(11):e223-e242.

[69] Chen Q, Xiao J, Lin Z, Xu X, Chen J. NAD+ supplement relieved chronic sleep restriction (CSR)-induced microglial proinflammation in vivo and in vitro. J Neuroimmunol. 2024; 397:578469.

[70] Sen P, Shah PP, Nativio R, Berger SL. Epigenetic mechanisms of longevity and aging. Cell. 2016; 166(4):822-839.

[71] Bi S, Liu Z, Wu Z, Wang Z, Liu X, Wang S, et al. SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer. Protein Cell. 2020; 11(7):483-504.

[72] Zhang H, Li J, Yu Y, Ren J, Liu Q, Bao Z, et al. Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging. Cell Rep. 2023; 42(11):113396.

[73] Liu X, Liu Z, Wu Z, Ren J, Fan Y, Sun L, et al. Resurrection of endogenous retroviruses during aging reinforces senescence. Cell. 2023; 186(2):287-304.e26.

[74] Sati S, Bonev B, Szabo Q, Jost D, Bensadoun P, Serra F, et al. 4D genome rewiring during oncogene-induced and replicative senescence. Mol Cell. 2020; 78(3):522-538.e9.

[75] Li X, Chen X, Zheng L, Chen M, Zhang Y, Zhu R, et al. Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-κB in inflammatory response. Acta Pharm Sin B. 2023; 13(12):4765-4784.

[76] Cancado de Faria R, Silva LND, Teodoro-Castro B, McCommis KS, Shashkova EV, Gonzalo S. A noncanonical cGAS-STING pathway drives cellular and organismal aging. Proc Natl Acad Sci U S A. 2025; 122(28):e2424666122.

[77] Liu H, Ghosh S, Vaidya T, Bammidi S, Huang C, Shang P, et al. Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy. JCI Insight. 2023; 8(12):e168945.

[78] Haj M, Levon A, Frey Y, Hourvitz N, Campisi J, Tzfati Y, et al. Accelerated replicative senescence of ataxia-telangiectasia skin fibroblasts is retained at physiologic oxygen levels, with unique and common transcriptional patterns. Aging Cell. 2023; 22(8):e13869.

[79] Vincent J, Adura C, Gao P, Luz A, Lama L, Asano Y, et al. Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice. Nat Commun. 2017; 8(1):750.

[80] Wang M, Sooreshjani MA, Mikek C, Opoku-Temeng C, Sintim HO. Suramin potently inhibits cGAMP synthase, cGAS, in THP1 cells to modulate IFN-β levels. Future Med Chem. 2018; 10(11):1301-1317.

[81] Hall J, Brault A, Vincent F, Weng S, Wang H, Dumlao D, et al. Discovery of PF-06928215 as a high affinity inhibitor of cGAS enabled by a novel fluorescence polarization assay. PLoS One. 2017; 12(9):e0184843.

[82] Udeochu JC, Amin S, Huang Y, Fan L, Torres ERS, Carling GK, et al. Tau activation of microglial cGAS-IFN reduces MEF2C-mediated cognitive resilience. Nat Neurosci. 2023; 26(5):737-750.

[83] Liu ZS, Cai H, Xue W, Wang M, Xia T, Li WJ, et al. G3BP1 promotes DNA binding and activation of cGAS. Nat Immunol. 2019; 20(1):18-28.

[84] Dai J, Huang YJ, He X, Zhao M, Wang X, Liu ZS, et al. Acetylation blocks cGAS activity and inhibits self-DNA-induced autoimmunity. Cell. 2019; 176(6):1447-1460.e14.

[85] Yu H, Liao K, Hu Y, Lv D, Luo M, Liu Q, et al. Role of the cGAS-STING pathway in aging-related endothelial dysfunction. Aging Dis. 2022; 13(6):1901.

[86] Gong Y, Li G, Tao J, Wu NN, Kandadi MR, Bi Y, et al. Double knockout of Akt2 and AMPK accentuates high fat diet-induced cardiac anomalies through a cGAS-STING-mediated mechanism. Biochim Biophys Acta Mol Basis Dis. 2020; 1866(10):165855.

[87] Dhingra R, Vasan RS. Age as a risk factor. Med Clin N Am. 2012; 96(1):87-91.

[88] Ribeiro-Filho HV, de Souza Silva CM, de Siqueira RJ, Lahlou S, dos Santos AA, Magalhães PJC. Biphasic cardiovascular and respiratory effects induced by β-citronellol. Eur J Pharmacol. 2016; 775:96-105.

[89] Naguib S, Lopez-Lee C, Torres ER, Lee SI, Zhu J, Zhu D, et al. The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway. Immunity. 2025; 58(8):1931-1947.e9.

[90] Bose D, Su Y, Marcus A, Raulet DH, Hammond MC. An RNA-based fluorescent biosensor for high-throughput analysis of the cGAS-cGAMP-STING pathway. Cell Chem Biol. 2016; 23(12):1539-1549.

[91] An J, Woodward JJ, Sasaki T, Minie M, Elkon KB. Cutting edge: Antimalarial drugs inhibit IFN-β production through blockade of cyclic GMP-AMP synthase-DNA interaction. J Immunol. 2015; 194(9):4089-4093.

[92] Haag SM, Gulen MF, Reymond L, Gibelin A, Abrami L, Decout A, et al. Targeting STING with covalent small-molecule inhibitors. Nature. 2018; 559(7713):269-273.

[93] Yan X, Wang E, Zhao M, Ma G, Xu XX, Zhao JB, et al. Microbial infection instigates tau-related pathology in Alzheimer’s disease via activating neuroimmune cGAS-STING pathway. Neuroscience. 2025; 572:122-133.

[94] Aguado J, Chaggar HK, Gómez-Inclán C, Shaker MR, Leeson HC, Mackay-Sim A, et al. Inhibition of the cGAS-STING pathway ameliorates the premature senescence hallmarks of Ataxia-Telangiectasia brain organoids. Aging Cell. 2021; 20(9):e13468.

[95] Hu S, Gao Y, Gao R, Wang Y, Qu Y, Yang JE, et al. The selective STING inhibitor H-151 preserves myocardial function and ameliorates cardiac fibrosis in murine myocardial infarction. Int Immunopharmacol. 2022; 107:108658.

[96] Hansen AL, Buchan GJ, Rühl M, Mukai K, Salvatore SR, Ogawa E, et al. Nitro-fatty acids are formed in response to virus infection and are potent inhibitors of STING palmitoylation and signaling. Proc Natl Acad Sci U S A. 2018; 115(33):E7768-E7775.

[97] Li S, Hong Z, Wang Z, Li F, Mei J, Huang L, et al. The cyclopeptide astin C specifically inhibits the innate immune CDN sensor STING. Cell Rep. 2018; 25(12):3405-3421.e7.

[98] Siu T, Altman MD, Baltus GA, Childers M, Ellis JM, Gunaydin H, et al. Discovery of a novel cGAMP competitive ligand of the inactive form of STING. ACS Med Chem Lett. 2019; 10(1):92-97.

[99] Austad SN, Ballinger S, Buford TW, Carter CS, Smith DL Jr, Darley-Usmar V, et al. Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer’s disease. Acta Pharm Sin B. 2022; 12(2):511-531.

[100] Myakala K, Wang XX, Shults NV, Krawczyk E, Jones BA, Yang X, et al. NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease. J Biol Chem. 2023; 299(8):104975.

[101] Wei P, Zhang X, Yan C, Sun S, Chen Z, Lin F. Mitochondrial dysfunction and aging: Multidimensional mechanisms and therapeutic strategies. Biogerontology. 2025; 26(4):142.

[102] Wan X, Tian J, Hao P, Zhang J, Zhou Y, Ge C, et al. The cGAS-STING pathway: A ubiquitous checkpoint perturbing myocardial attributes. Curr Vasc Pharmacol. 2023; 21(3):152-162.