Top

Published in:

Open Access 01-12-2024 | Review

The role of NLRP3 inflammasome in aging and age-related diseases

Authors: Ruikai Liang, Xinrui Qi, Qi Cai, Liyan Niu, Xi Huang, Deju Zhang, Jitao Ling, Yuting Wu, Yixuan Chen, Pingping Yang, Jianping Liu, Jing Zhang, Peng Yu

Published in: Immunity & Ageing | Issue 1/2024

Abstract

The gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms.

Kanasi E, Ayilavarapu S, Jones J. The aging population: demographics and the biology of aging. Periodontol 2000. 2016;72(1):13–8. https://doi.org/10.1111/prd.12126.CrossRefPubMed

Riera CE, Dillin A. Can aging be “drugged”? Nat Med. 2015;21(12):1400–5. https://doi.org/10.1038/nm.4005.

Van Avondt K, Strecker JK, Tulotta C, Minnerup J, Schulz C, Soehnlein O. Neutrophils in aging and aging-related pathologies. Immunol Rev. 2023;314(1):357–75. https://doi.org/10.1111/imr.13153.CrossRefPubMed

Gritsenko A, Green JP, Brough D, Lopez-Castejon G. Mechanisms of NLRP3 priming in inflammaging and age related diseases. Cytokine Growth Factor Rev. 2020;55:15–25. https://doi.org/10.1016/j.cytogfr.2020.08.003.CrossRefPubMedPubMedCentral

Allen JC, Toapanta FR, Chen W, Tennant SM. Understanding immunosenescence and its impact on vaccination of older adults. Vaccine. 2020;38(52):8264–72. https://doi.org/10.1016/j.vaccine.2020.11.002.CrossRefPubMedPubMedCentral

Liu Y, Xu X, Lei W, et al. The NLRP3 inflammasome in fibrosis and aging: The known unknowns. Ageing Res Rev. 2022;79: 101638. https://doi.org/10.1016/j.arr.2022.101638.CrossRefPubMed

Goldberg EL, Dixit VD. Drivers of age-related inflammation and strategies for healthspan extension. Immunol Rev. 2015;265(1):63–74. https://doi.org/10.1111/imr.12295.CrossRefPubMedPubMedCentral

Ma Q. Pharmacological Inhibition of the NLRP3 Inflammasome: Structure, Molecular Activation, and Inhibitor-NLRP3 Interaction. Pharmacol Rev. 2023;75(3):487–520. https://doi.org/10.1124/pharmrev.122.000629.CrossRefPubMed

Lee KA, Robbins PD, Camell CD. Intersection of immunometabolism and immunosenescence during aging. Curr Opin Pharmacol. 2021;57:107–16. https://doi.org/10.1016/j.coph.2021.01.003.CrossRefPubMedPubMedCentral

10.

Höhn A, Weber D, Jung T, et al. Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence. Redox Biol. 2017;11:482–501. https://doi.org/10.1016/j.redox.2016.12.001.CrossRefPubMed

11.

Fujita K. p53 Isoforms in Cellular Senescence- and Ageing-Associated Biological and Physiological Functions. Int J Mol Sci. 2019;20(23). https://doi.org/10.3390/ijms20236023.

12.

Gorgoulis V, Adams PD, Alimonti A, et al. Cellular Senescence: Defining a Path Forward. Cell. 2019;179(4):813–27. https://doi.org/10.1016/j.cell.2019.10.005.CrossRefPubMed

13.

Childs BG, Durik M, Baker DJ, van Deursen JM. Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med. 2015;21(12):1424–35. https://doi.org/10.1038/nm.4000.CrossRefPubMedPubMedCentral

14.

Calcinotto A, Kohli J, Zagato E, Pellegrini L, Demaria M, Alimonti A. Cellular Senescence: Aging, Cancer, and Injury. Physiol Rev. 2019;99(2):1047–78. https://doi.org/10.1152/physrev.00020.2018.CrossRefPubMed

15.

He S, Sharpless NE. Senescence in Health and Disease. Cell. 2017;169(6):1000–11. https://doi.org/10.1016/j.cell.2017.05.015.CrossRefPubMedPubMedCentral

16.

Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of Cellular Senescence. Trends Cell Biol. 2018;28(6):436–53. https://doi.org/10.1016/j.tcb.2018.02.001.CrossRefPubMed

17.

Currais A, Fischer W, Maher P, Schubert D. Intraneuronal protein aggregation as a trigger for inflammation and neurodegeneration in the aging brain. FASEB J. 2017;31(1):5–10. https://doi.org/10.1096/fj.201601184.CrossRefPubMed

18.

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):576–90. https://doi.org/10.1038/s41574-018-0059-4.CrossRefPubMed

19.

Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA. Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Front Immunol. 2018;9:586. https://doi.org/10.3389/fimmu.2018.00586.CrossRefPubMedPubMedCentral

20.

Chistiakov DA, Melnichenko AA, Grechko AV, Myasoedova VA, Orekhov AN. Potential of anti-inflammatory agents for treatment of atherosclerosis. Exp Mol Pathol. 2018;104(2):114–24. https://doi.org/10.1016/j.yexmp.2018.01.008.CrossRefPubMed

21.

Camici GG, Savarese G, Akhmedov A, Lüscher TF. Molecular mechanism of endothelial and vascular aging: implications for cardiovascular disease. Eur Heart J. 2015;36(48):3392–403. https://doi.org/10.1093/eurheartj/ehv587.CrossRefPubMed

22.

Bai J, Yang F, Dong L, Zheng Y. Ghrelin Protects Human Lens Epithelial Cells against Oxidative Stress-Induced Damage. Oxid Med Cell Longev. 2017;2017:1910450. https://doi.org/10.1155/2017/1910450.CrossRefPubMedPubMedCentral

23.

Jo S, Yarishkin O, Hwang YJ, et al. GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease. Nat Med. 2014;20(8):886–96. https://doi.org/10.1038/nm.3639.

24.

Khosla S, Farr JN, Tchkonia T, Kirkland JL. The role of cellular senescence in ageing and endocrine disease. Nat Rev Endocrinol. 2020;16(5):263–75. https://doi.org/10.1038/s41574-020-0335-y.CrossRefPubMed

25.

Baker DJ, Petersen RC. Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives. J Clin Investig. 2018;128(4):1208–16. https://doi.org/10.1172/jci95145.CrossRefPubMedPubMedCentral

26.

Farr JN, Fraser DG, Wang H, et al. Identification of Senescent Cells in the Bone Microenvironment. J Bone Miner Res. 2016;31(11):1920–9. https://doi.org/10.1002/jbmr.2892.CrossRefPubMed

27.

Wang R, Wang Y, Zhu L, Liu Y, Li W. Epigenetic Regulation in Mesenchymal Stem Cell Aging and Differentiation and Osteoporosis. Stem Cells Int. 2020;2020:8836258. https://doi.org/10.1155/2020/8836258.CrossRefPubMedPubMedCentral

28.

Coppé JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010;5:99–118. https://doi.org/10.1146/annurev-pathol-121808-102144.CrossRefPubMedPubMedCentral

29.

Sharma BR, Kanneganti TD. NLRP3 inflammasome in cancer and metabolic diseases. Nat Immunol. 2021;22(5):550–9. https://doi.org/10.1038/s41590-021-00886-5.CrossRefPubMedPubMedCentral

30.

Meyers AK, Zhu X. The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging. Cells. 2020;9(8). https://doi.org/10.3390/cells9081808.

31.

Camell CD, Günther P, Lee A, et al. Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis. Cell Metab. 2019;30(6):1024–1039.e6. https://doi.org/10.1016/j.cmet.2019.10.006.CrossRefPubMedPubMedCentral

32.

Navarro-Pando JM, Alcocer-Gómez E, Castejón-Vega B, et al. Inhibition of the NLRP3 inflammasome prevents ovarian aging. Sci Adv. 2021;7(1). https://doi.org/10.1126/sciadv.abc7409.

33.

Li D, Liu M, Li Z, et al. Sterol-resistant SCAP Overexpression in Vascular Smooth Muscle Cells Accelerates Atherosclerosis by Increasing Local Vascular Inflammation through Activation of the NLRP3 Inflammasome in Mice. Aging Dis. 2021;12(3):747–63. https://doi.org/10.14336/ad.2020.1120.CrossRefPubMedPubMedCentral

34.

Murakami T, Nakaminami Y, Takahata Y, Hata K, Nishimura R. Activation and Function of NLRP3 Inflammasome in Bone and Joint-Related Diseases. Int J Mol Sci. 2022;23(10). https://doi.org/10.3390/ijms23105365.

35.

Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018;15(9):505–22. https://doi.org/10.1038/s41569-018-0064-2.CrossRefPubMedPubMedCentral

36.

Orecchioni M, Kobiyama K, Winkels H, et al. Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production. Science. 2022;375(6577):214–21. https://doi.org/10.1126/science.abg3067.ADSCrossRefPubMedPubMedCentral

37.

Kosuru R, Kandula V, Rai U, Prakash S, Xia Z, Singh S. Pterostilbene Decreases Cardiac Oxidative Stress and Inflammation via Activation of AMPK/Nrf2/HO-1 Pathway in Fructose-Fed Diabetic Rats. Cardiovasc Drugs Ther. 2018;32(2):147–63. https://doi.org/10.1007/s10557-018-6780-3.CrossRefPubMed

38.

Zhang J, Huang L, Shi X, et al. Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK/NLRP3 inflammasome pathway. Aging (Albany NY). 2020;12(23):24270–87. https://doi.org/10.18632/aging.202143.CrossRefPubMed

39.

Ye Y, Jin T, Zhang X, et al. Meisoindigo Protects Against Focal Cerebral Ischemia-Reperfusion Injury by Inhibiting NLRP3 Inflammasome Activation and Regulating Microglia/Macrophage Polarization via TLR4/NF-κB Signaling Pathway. Front Cell Neurosci. 2019;13:553. https://doi.org/10.3389/fncel.2019.00553.CrossRefPubMedPubMedCentral

40.

Sano S, Oshima K, Wang Y, et al. Tet2-Mediated Clonal Hematopoiesis Accelerates Heart Failure Through a Mechanism Involving the IL-1β/NLRP3 Inflammasome. J Am Coll Cardiol. 2018;71(8):875–86. https://doi.org/10.1016/j.jacc.2017.12.037.CrossRefPubMedPubMedCentral

41.

Aliaga J, Bonaventura A, Mezzaroma E, et al. Preservation of Contractile Reserve and Diastolic Function by Inhibiting the NLRP3 Inflammasome with OLT1177(®) (Dapansutrile) in a Mouse Model of Severe Ischemic Cardiomyopathy Due to Non-Reperfused Anterior Wall Myocardial Infarction. Molecules. 2021;26(12). https://doi.org/10.3390/molecules26123534.

42.

Riehle C, Bauersachs J. Key inflammatory mechanisms underlying heart failure. Herz. 2019;44(2):96–106. https://doi.org/10.1007/s00059-019-4785-8. (Entzündungsmechanismen bei Herzinsuffizienz).CrossRefPubMedPubMedCentral

43.

Dick SA, Epelman S. Chronic Heart Failure and Inflammation: What Do We Really Know? Circ Res. 2016;119(1):159–76. https://doi.org/10.1161/circresaha.116.308030.CrossRefPubMed

44.

Heymans S, Hirsch E, Anker SD, et al. Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2009;11(2):119–29. https://doi.org/10.1093/eurjhf/hfn043.CrossRefPubMedPubMedCentral

45.

Ong SB, Hernández-Reséndiz S, Crespo-Avilan GE, et al. Inflammation following acute myocardial infarction: Multiple players, dynamic roles, and novel therapeutic opportunities. Pharmacol Ther. 2018;186:73–87. https://doi.org/10.1016/j.pharmthera.2018.01.001.CrossRefPubMedPubMedCentral

46.

Suetomi T, Miyamoto S, Brown JH. Inflammation in nonischemic heart disease: initiation by cardiomyocyte CaMKII and NLRP3 inflammasome signaling. Am J Physiol Heart Circ Physiol. 2019;317(5):H877–h890. https://doi.org/10.1152/ajpheart.00223.2019.CrossRefPubMedPubMedCentral

47.

Luo B, Wang F, Li B, et al. Association of nucleotide-binding oligomerization domain-like receptor 3 inflammasome and adverse clinical outcomes in patients with idiopathic dilated cardiomyopathy. Clin Chem Lab Med. 2013;51(7):1521–8. https://doi.org/10.1515/cclm-2012-0600.CrossRefPubMed

48.

Zeng C, Duan F, Hu J, et al. NLRP3 inflammasome-mediated pyroptosis contributes to the pathogenesis of non-ischemic dilated cardiomyopathy. Redox Biol. 2020;34: 101523. https://doi.org/10.1016/j.redox.2020.101523.CrossRefPubMedPubMedCentral

49.

Bhatia R, Holtan S, Jurdi NE, Prizment A, Blaes A. Do Cancer and Cancer Treatments Accelerate Aging? Curr Oncol Rep. 2022;24(11):1401–12. https://doi.org/10.1007/s11912-022-01311-2.CrossRefPubMedPubMedCentral

50.

Xu Z, Wang H, Qin Z, et al. NLRP3 inflammasome promoted the malignant progression of prostate cancer via the activation of caspase-1. Cell Death Discov. 2021;7(1):399. https://doi.org/10.1038/s41420-021-00766-9.CrossRefPubMedPubMedCentral

51.

Zhao AN, Yang Z, Wang DD, et al. Disturbing NLRP3 acetylation and inflammasome assembly inhibits androgen receptor-promoted inflammatory responses and prostate cancer progression. FASEB J. 2022;36(11):e22602. https://doi.org/10.1096/fj.202200673RRR.CrossRefPubMed

52.

Di Mitri D, Mirenda M, Vasilevska J, et al. Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer. Cell Rep. 2019;28(8):2156–2168.e5. https://doi.org/10.1016/j.celrep.2019.07.068.CrossRefPubMedPubMedCentral

53.

Guerriero JL, Sotayo A, Ponichtera HE, et al. Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature. 2017;543(7645):428–32. https://doi.org/10.1038/nature21409.ADSCrossRefPubMedPubMedCentral

54.

Liang M, Chen X, Wang L, et al. Cancer-derived exosomal TRIM59 regulates macrophage NLRP3 inflammasome activation to promote lung cancer progression. J Exp Clin Cancer Res. 2020;39(1):176. https://doi.org/10.1186/s13046-020-01688-7.CrossRefPubMedPubMedCentral

55.

Wang L, Zhang LF, Wu J, et al. IL-1β-mediated repression of microRNA-101 is crucial for inflammation-promoted lung tumorigenesis. Cancer Res. 2014;74(17):4720–30. https://doi.org/10.1158/0008-5472.Can-14-0960.CrossRefPubMed

56.

Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P, Glynn RJ. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390(10105):1833–42. https://doi.org/10.1016/s0140-6736(17)32247-x.CrossRefPubMed

57.

Ma W, Wang Z, Zhao Y, et al. Salidroside Suppresses the Proliferation and Migration of Human Lung Cancer Cells through AMPK-Dependent NLRP3 Inflammasome Regulation. Oxid Med Cell Longev. 2021;2021:6614574. https://doi.org/10.1155/2021/6614574.CrossRefPubMedPubMedCentral

58.

Alsaadi M, Tezcan G, Garanina EE, et al. Doxycycline Attenuates Cancer Cell Growth by Suppressing NLRP3-Mediated Inflammation. Pharmaceuticals (Basel). 2021;14(9). https://doi.org/10.3390/ph14090852.

59.

Arana Echarri A, Beresford M, Campbell JP, et al. A Phenomic Perspective on Factors Influencing Breast Cancer Treatment: Integrating Aging and Lifestyle in Blood and Tissue Biomarker Profiling. Front Immunol. 2020;11:616188. https://doi.org/10.3389/fimmu.2020.616188.CrossRefPubMed

60.

Wellenstein MD, Coffelt SB, Duits DEM, et al. Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis. Nature. 2019;572(7770):538–42. https://doi.org/10.1038/s41586-019-1450-6.ADSCrossRefPubMedPubMedCentral

61.

Takenaka MC, Robson S, Quintana FJ. Regulation of the T Cell Response by CD39. Trends Immunol. 2016;37(7):427–39. https://doi.org/10.1016/j.it.2016.04.009.CrossRefPubMedPubMedCentral

62.

Ershaid N, Sharon Y, Doron H, et al. NLRP3 inflammasome in fibroblasts links tissue damage with inflammation in breast cancer progression and metastasis. Nat Commun. 2019;10(1):4375. https://doi.org/10.1038/s41467-019-12370-8.ADSCrossRefPubMedPubMedCentral

63.

Vecchié A, Del Buono MG, Chiabrando GJ, Dentali F, Abbate A, Bonaventura A. Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease. Curr Cardiol Rep. 2021;23(11):157. https://doi.org/10.1007/s11886-021-01589-x.CrossRefPubMedPubMedCentral

64.

Li T, Fu B, Zhang X, et al. Overproduction of Gastrointestinal 5-HT Promotes Colitis-Associated Colorectal Cancer Progression via Enhancing NLRP3 Inflammasome Activation. Cancer Immunol Res. 2021;9(9):1008–23. https://doi.org/10.1158/2326-6066.Cir-20-1043.CrossRefPubMed

65.

Wang H, Wang Y, Du Q, et al. Inflammasome-independent NLRP3 is required for epithelial-mesenchymal transition in colon cancer cells. Exp Cell Res. 2016;342(2):184–92. https://doi.org/10.1016/j.yexcr.2016.03.009.MathSciNetCrossRefPubMed

66.

Dagenais M, Saleh M. Linking cancer-induced Nlrp3 inflammasome activation to efficient NK cell-mediated immunosurveillance. Oncoimmunology. 2016;5(5):e1129484. https://doi.org/10.1080/2162402x.2015.1129484.CrossRefPubMedPubMedCentral

67.

Newton K, Dixit VM, Kayagaki N. Dying cells fan the flames of inflammation. Science. 2021;374(6571):1076–80. https://doi.org/10.1126/science.abi5934.ADSCrossRefPubMed

68.

An S, Hu H, Li Y, Hu Y. Pyroptosis Plays a Role in Osteoarthritis. Aging Dis. 2020;11(5):1146–57. https://doi.org/10.14336/ad.2019.1127.CrossRefPubMedPubMedCentral

69.

Unterberger S, Davies KA, Rambhatla SB, Sacre S. Contribution of Toll-Like Receptors and the NLRP3 Inflammasome in Rheumatoid Arthritis Pathophysiology. Immunotargets Ther. 2021;10:285–98. https://doi.org/10.2147/itt.S288547.CrossRefPubMedPubMedCentral

70.

Sokolove J, Zhao X, Chandra PE, Robinson WH. Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcγ receptor. Arthritis Rheum. 2011;63(1):53–62. https://doi.org/10.1002/art.30081.CrossRefPubMedPubMedCentral

71.

Fan W, Chen S, Wu X, Zhu J, Li J. Resveratrol Relieves Gouty Arthritis by Promoting Mitophagy to Inhibit Activation of NLRP3 Inflammasomes. J Inflamm Res. 2021;14:3523–36. https://doi.org/10.2147/jir.S320912.CrossRefPubMedPubMedCentral

72.

Zhang Y, Jiao Y, Li X, et al. Pyroptosis: A New Insight Into Eye Disease Therapy. Front Pharmacol. 2021;12: 797110. https://doi.org/10.3389/fphar.2021.797110.CrossRefPubMedPubMedCentral

73.

Teng H, Hong YR, Li H, et al. Pyroptosis of lens epithelial cells in diabetic cataract. Zhonghua Yan Ke Za Zhi. 2022;58(5):354–9. https://doi.org/10.3760/cma.j.cn112142-20211021-00493.CrossRefPubMed

74.

Sun Y, Rong X, Li D, Jiang Y, Lu Y, Ji Y. Down-regulation of CRTAC1 attenuates UVB-induced pyroptosis in HLECs through inhibiting ROS production. Biochem Biophys Res Commun. 2020;532(1):159–65. https://doi.org/10.1016/j.bbrc.2020.07.028.CrossRefPubMed

75.

Marneros AG. Increased VEGF-A promotes multiple distinct aging diseases of the eye through shared pathomechanisms. EMBO Mol Med. 2016;8(3):208–31. https://doi.org/10.15252/emmm.201505613.CrossRefPubMedPubMedCentral

76.

Jiang N, An J, Yang K, et al. NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis? Front Endocrinol (Lausanne). 2021;12: 752546. https://doi.org/10.3389/fendo.2021.752546.CrossRefPubMed

77.

Cline-Smith A, Axelbaum A, Shashkova E, et al. Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice. J Bone Miner Res. 2020;35(6):1174–87. https://doi.org/10.1002/jbmr.3966.CrossRefPubMed

78.

Khosla S, Hofbauer LC. Osteoporosis treatment: recent developments and ongoing challenges. Lancet Diabetes Endocrinol. 2017;5(11):898–907. https://doi.org/10.1016/s2213-8587(17)30188-2.CrossRefPubMedPubMedCentral

79.

Sartoretto S, Gemini-Piperni S, da Silva RA, et al. Apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) contributes to osteoblast differentiation and osteogenesis. J Cell Physiol. 2019;234(4):4140–53. https://doi.org/10.1002/jcp.27226.CrossRefPubMed

80.

Snouwaert JN, Nguyen M, Repenning PW, et al. An NLRP3 Mutation Causes Arthropathy and Osteoporosis in Humanized Mice. Cell Rep. 2016;17(11):3077–88. https://doi.org/10.1016/j.celrep.2016.11.052.CrossRefPubMed

81.

Palmer AK, Gustafson B, Kirkland JL, Smith U. Cellular senescence: at the nexus between ageing and diabetes. Diabetologia. 2019;62(10):1835–41. https://doi.org/10.1007/s00125-019-4934-x.CrossRefPubMedPubMedCentral

82.

Schroder K, Zhou R, Tschopp J. The NLRP3 inflammasome: a sensor for metabolic danger? Science. 2010;327(5963):296–300. https://doi.org/10.1126/science.1184003.ADSCrossRefPubMed

83.

Masters SL, Dunne A, Subramanian SL, et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nat Immunol. 2010;11(10):897–904. https://doi.org/10.1038/ni.1935.CrossRefPubMedPubMedCentral

84.

Tsuji G, Hashimoto-Hachiya A, Yen VH, et al. Metformin inhibits IL-1β secretion via impairment of NLRP3 inflammasome in keratinocytes: implications for preventing the development of psoriasis. Cell Death Discov. 2020;6:11. https://doi.org/10.1038/s41420-020-0245-8.CrossRefPubMedPubMedCentral

85.

Buford TW. Hypertension and aging. Ageing Res Rev. 2016;26:96–111. https://doi.org/10.1016/j.arr.2016.01.007.CrossRefPubMedPubMedCentral

86.

Bautista LE, Atwood JE, O’Malley PG, Taylor AJ. Association between C-reactive protein and hypertension in healthy middle-aged men and women. Coron Artery Dis. 2004;15(6):331–6. https://doi.org/10.1097/00019501-200409000-00006.

87.

Stuveling EM, Bakker SJ, Hillege HL, et al. C-reactive protein modifies the relationship between blood pressure and microalbuminuria. Hypertension. 2004;43(4):791–6. https://doi.org/10.1161/01.Hyp.0000120125.08867.42.CrossRefPubMed

88.

Sun HJ, Ren XS, Xiong XQ, et al. NLRP3 inflammasome activation contributes to VSMC phenotypic transformation and proliferation in hypertension. Cell Death Dis. 2017;8(10):e3074. https://doi.org/10.1038/cddis.2017.470.CrossRefPubMedPubMedCentral

89.

Zhu J, Yang Y, Hu SG, Zhang QB, Yu J, Zhang YM. T-lymphocyte K(v)1.3 channel activation triggers the NLRP3 inflammasome signaling pathway in hypertensive patients. Exp Ther Med. 2017;14(1):147–54. https://doi.org/10.3892/etm.2017.4490.CrossRefPubMedPubMedCentral

90.

Hosokawa S, Haraguchi G, Sasaki A, et al. Pathophysiological roles of nuclear factor kappaB (NF-kB) in pulmonary arterial hypertension: effects of synthetic selective NF-kB inhibitor IMD-0354. Cardiovasc Res. 2013;99(1):35–43. https://doi.org/10.1093/cvr/cvt105.CrossRefPubMed

91.

Qi J, Yu XJ, Shi XL, et al. NF-κB Blockade in Hypothalamic Paraventricular Nucleus Inhibits High-Salt-Induced Hypertension Through NLRP3 and Caspase-1. Cardiovasc Toxicol. 2016;16(4):345–54. https://doi.org/10.1007/s12012-015-9344-9.CrossRefPubMed

92.

Krishnan SM, Ling YH, Huuskes BM, et al. Pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure, renal damage, and dysfunction in salt-sensitive hypertension. Cardiovasc Res. 2019;115(4):776–87. https://doi.org/10.1093/cvr/cvy252.CrossRefPubMed

93.

Mattson MP, Arumugam TV. Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States. Cell Metab. 2018;27(6):1176–99. https://doi.org/10.1016/j.cmet.2018.05.011.CrossRefPubMedPubMedCentral

94.

Holbrook JA, Jarosz-Griffiths HH, Caseley E, et al. Neurodegenerative Disease and the NLRP3 Inflammasome. Front Pharmacol. 2021;12:643254. https://doi.org/10.3389/fphar.2021.643254.CrossRefPubMedPubMedCentral

95.

Xu TT, Li H, Dai Z, et al. Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice. Aging (Albany NY). 2020;12(7):6401–14. https://doi.org/10.18632/aging.103035.CrossRefPubMed

96.

Mazaheri-Tehrani E, Mohraz M, Nasi M, et al. NLRP3 and IL-1β Gene Expression Is Elevated in Monocytes From HIV-Treated Patients With Neurocognitive Disorders. J Acquir Immune Defic Syndr. 2021;86(4):496–9. https://doi.org/10.1097/qai.0000000000002588.CrossRefPubMed

97.

Heneka MT, Kummer MP, Stutz A, et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature. 2013;493(7434):674–8. https://doi.org/10.1038/nature11729.

98.

Blum-Degen D, Müller T, Kuhn W, Gerlach M, Przuntek H, Riederer P. Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett. 1995;202(1–2):17–20. https://doi.org/10.1016/0304-3940(95)12192-7.

99.

Saresella M, La Rosa F, Piancone F, et al. The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer’s disease. Mol Neurodegener. 2016;11:23. https://doi.org/10.1186/s13024-016-0088-1.

100.

Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating CE, Joers V. Inflammation and immune dysfunction in Parkinson disease. Nat Rev Immunol. 2022;22(11):657–73. https://doi.org/10.1038/s41577-022-00684-6.CrossRefPubMedPubMedCentral

101.

Fan XM, Luo Y, Cao YM, et al. Chronic Manganese Administration with Longer Intervals Between Injections Produced Neurotoxicity and Hepatotoxicity in Rats. Neurochem Res. 2020;45(8):1941–52. https://doi.org/10.1007/s11064-020-03059-2.CrossRefPubMedPubMedCentral

102.

Chen C, Wei YZ, He XM, et al. Naringenin Produces Neuroprotection Against LPS-Induced Dopamine Neurotoxicity via the Inhibition of Microglial NLRP3 Inflammasome Activation. Front Immunol. 2019;10:936. https://doi.org/10.3389/fimmu.2019.00936.CrossRefPubMedPubMedCentral

103.

Han C, Shen H, Yang Y, et al. Antrodia camphorata polysaccharide resists 6-OHDA-induced dopaminergic neuronal damage by inhibiting ROS-NLRP3 activation. Brain Behav. 2020;10(11):e01824. https://doi.org/10.1002/brb3.1824.CrossRefPubMedPubMedCentral

104.

Leem YH, Park JS, Park JE, Kim DY, Kim HS. Papaverine Exerts Neuroprotective Effect by Inhibiting NLRP3 Inflammasome Activation in an MPTP-Induced Microglial Priming Mouse Model Challenged with LPS. Biomol Ther (Seoul). 2021;29(3):295–302. https://doi.org/10.4062/biomolther.2021.039.CrossRefPubMed

105.

Liu Q, Guo X, Huang Z, et al. Anti-neuroinflammatory effects of dimethylaminomylide (DMAMCL, i.e., ACT001) are associated with attenuating the NLRP3 inflammasome in MPTP-induced Parkinson disease in mice. Behav Brain Res. 2020;383:112539. https://doi.org/10.1016/j.bbr.2020.112539.CrossRefPubMed

106.

Sarkar S, Malovic E, Harishchandra DS, et al. Mitochondrial impairment in microglia amplifies NLRP3 inflammasome proinflammatory signaling in cell culture and animal models of Parkinson’s disease. NPJ Parkinsons Dis. 2017;3:30. https://doi.org/10.1038/s41531-017-0032-2.

107.

Yan Y, Jiang W, Liu L, et al. Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell. 2015;160(1–2):62–73. https://doi.org/10.1016/j.cell.2014.11.047.CrossRefPubMed

108.

Li L, Xiong WC, Mei L. Neuromuscular Junction Formation, Aging, and Disorders. Annu Rev Physiol. 2018;80:159–88. https://doi.org/10.1146/annurev-physiol-022516-034255.CrossRefPubMed

109.

Pandya VA, Patani R. Decoding the relationship between ageing and amyotrophic lateral sclerosis: a cellular perspective. Brain. 2020;143(4):1057–72. https://doi.org/10.1093/brain/awz360.CrossRefPubMed

110.

Italiani P, Carlesi C, Giungato P, et al. Evaluating the levels of interleukin-1 family cytokines in sporadic amyotrophic lateral sclerosis. J Neuroinflammation. 2014;11:94. https://doi.org/10.1186/1742-2094-11-94.CrossRefPubMedPubMedCentral

111.

Zhao W, Beers DR, Hooten KG, et al. Characterization of Gene Expression Phenotype in Amyotrophic Lateral Sclerosis Monocytes. JAMA Neurol. 2017;74(6):677–85. https://doi.org/10.1001/jamaneurol.2017.0357.CrossRefPubMedPubMedCentral

112.

Zhang C, Wang H, Liang W, et al. Diphenyl diselenide protects motor neurons through inhibition of microglia-mediated inflammatory injury in amyotrophic lateral sclerosis. Pharmacol Res. 2021;165:105457. https://doi.org/10.1016/j.phrs.2021.105457.CrossRefPubMed

113.

Fabbrizio P, Apolloni S, Bianchi A, et al. P2X7 activation enhances skeletal muscle metabolism and regeneration in SOD1G93A mouse model of amyotrophic lateral sclerosis. Brain Pathol. 2020;30(2):272–82. https://doi.org/10.1111/bpa.12774.CrossRefPubMed

Title: The role of NLRP3 inflammasome in aging and age-related diseases
Authors: Ruikai Liang
Xinrui Qi
Qi Cai
Liyan Niu
Xi Huang
Deju Zhang
Jitao Ling
Yuting Wu
Yixuan Chen
Pingping Yang
Jianping Liu
Jing Zhang
Peng Yu
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: Immunity & Ageing / Issue 1/2024
Electronic ISSN: 1742-4933
DOI: https://doi.org/10.1186/s12979-023-00395-z

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2024

Longevity-associated BPIFB4 gene counteracts the inflammatory signaling

Helicobacter pylori infection and Parkinson’s Disease: etiology, pathogenesis and levodopa bioavailability

Chitosan alleviates ovarian aging by enhancing macrophage phagocyte-mediated tissue homeostasis

An aging-related immune landscape in the hematopoietic immune system

Changes in the innate immune response to SARS-CoV-2 with advancing age in humans

Quercetin promotes the proportion and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage