Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states
Open accessAbstract
Low-grade, chronic inflammation has been associated with many diseases of aging, but the mechanisms responsible for producing this inflammation remain unclear. Inflammasomes can drive chronic inflammation in the context of an infectious disease or cellular stress, and they trigger the maturation of interleukin-1β (IL-1β). Here we find that the expression of specific inflammasome gene modules stratifies older individuals into two extremes: those with constitutive expression of IL-1β, nucleotide metabolism dysfunction, elevated oxidative stress, high rates of hypertension and arterial stiffness; and those without constitutive expression of IL-1β, who lack these characteristics. Adenine and N 4-acetylcytidine, nucleotide-derived metabolites that are detectable in the blood of the former group, prime and activate the NLRC4 inflammasome, induce the production of IL-1β, activate platelets and neutrophils and elevate blood pressure in mice. In individuals over 85 years of age, the elevated expression of inflammasome gene modules was associated with all-cause mortality. Thus, targeting inflammasome components may ameliorate chronic inflammation and various other age-associated conditions.
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Inflammation promotes oxidation through inflammatory mediators.
“At the same time, inflammation promotes oxidation through inflammatory mediators.205,206”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [205]
The Discussion describes the opposite causal direction: oxidative stress triggers an inflammatory response, including production of inflammatory cytokines. The Results attribute chronic oxidative stress to possible mitochondrial metabolic reprogramming, not to inflammatory mediators. Page numbers are unavailable in our copy. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredA shift from short-lived to long-lived inflammation can break immune tolerance and alter tissues, organs, and cellular physiology, raising the risk of non-communicable diseases in both young and older people.
“Shifts in the inflammatory response from short- to long-lived can cause a breakdown of immune tolerance9,15 and lead to major alterations in all tissues and organs, as well as normal cellular physiology, which can increase the risk for various non-communicable diseases in both young and older individuals1,9–11,15,17–21.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [1]
Systemic chronic inflammation often increases with age, as older individuals have higher circulating cytokines, chemokines, acute phase proteins, and inflammatory gene expression.
“SCI often increases with age30, as indicated by studies showing that older individuals have higher circulating levels of cytokines, chemokines and acute phase proteins, as well as greater expression of genes involved in inflammation1,19,30.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [1]
Systemic chronic inflammation is low-grade and persistent and causes collateral damage to tissues and organs over time, including oxidative stress.
“SCI is low-grade and persistent (as the name suggests) and ultimately causes collateral damage to tissues and organs over time, such as by inducing oxidative stress1,4,9,19.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [1]
These altered molecules increase with age and can act as DAMPs that innate immune cells detect, activating the inflammasome machinery, amplifying inflammation, and contributing to inflammaging.
“These altered molecules, which increase with age19,30, can be recognized as DAMPs by innate immune cells, which in turn activate the inflammasome machinery, amplify the inflammatory response1,30,60 and contribute to a biological state that has been called “inflammaging,””
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [1]
Cytokine stimulation assays have proven utility for assessing overall immune competence.
“Despite the proven utility of cytokine stimulation assays used in our study with respect to an individual’s overall immune competence5,24,25”
From An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging (2021) · cites this paper as [5]
Systemic low-grade chronic inflammation that develops with age, referred to as inflammaging, appears to affect the phenotype and function of CD4 T cells.
“In addition, systemic low-grade chronic inflammation that develops with age, referred to as “inflammaging”, also appears to affect the phenotype and function of CD4 T cells (14, 15).”
From Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes (2019) · cites this paper as [15]
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Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
In silico prediction of protein-protein interactions in human macrophages
Souiai, O., Guerfali, F. Z., Miled, S. B., Brun, C., & Benkahla, A. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-157 · Cited by 10,785 · see citing works
Significance analysis of microarrays applied to the ionizing radiation response
Tusher, V. G., Tibshirani, R., & Chu, G. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091062498 · Cited by 10,568 · see citing works
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066 · see citing works
A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602 · see citing works
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026 · see citing works
Data, information, knowledge and principle: back to metabolism in KEGG
Kanehisa, M. I., Goto, S., Sato, Y., Kawashima, M., Furumichi, M., & Tanabe, M. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1076 · Cited by 3,103 · see citing works
The Reference Values for Arterial Stiffness' Collaboration (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq165 · Cited by 2,085 · see citing works
The Immunological Genome Project: networks of gene expression in immune cells
The Immunological Genome Project Consortium, Heng, T. S. P., Painter, M. W., Elpek, K., Lukacs-Kornek, V., Mauermann, N., Turley, S. J., Koller, D., Kim, F. S., Wagers, A. J., et al. (2008) · Nature Immunology · doi:10.1038/ni1008-1091 · Cited by 1,864 · see citing works
STEM: a tool for the analysis of short time series gene expression data
Ernst, J., & Bar-Joseph, Z. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-191 · Cited by 1,703 · see citing works
Segal, E., Shapira, M., Regev, A., Pe’er, D., Botstein, D., Koller, D., & Friedman, N. (2003) · Nature Genetics · doi:10.1038/ng1165 · Cited by 1,686 · see citing works
An atlas of genetic influences on human blood metabolites
The Multiple Tissue Human Expression Resource (MuTHER) Consortium, Shin, S.-Y., Fauman, E. B., Petersen, A.-K., Krumsiek, J., Santos, R., Huang, J., Arnold, M., Erte, I., Forgetta, V., et al. (2014) · Nature Genetics · doi:10.1038/ng.2982 · Cited by 1,515 · see citing works
Homeostasis, Inflammation, and Disease Susceptibility
Kotas, M. E., & Medzhitov, R. (2015) · Cell · doi:10.1016/j.cell.2015.02.010 · Cited by 1,213 · see citing works
Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression
Nelson, D. E., Ihekwaba, A. E. C., Elliott, M., Johnson, J. R., Gibney, C. A., Foreman, B. E., Nelson, G., See, V., Horton, C. A., Spiller, D. G., et al. (2004) · Science · doi:10.1126/science.1099962 · Cited by 1,186 · see citing works
Inflammasomes and Their Roles in Health and Disease
Lamkanfi, M., & Dixit, V. M. (2012) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155745 · Cited by 935 · see citing works
MetPA: a web-based metabolomics tool for pathway analysis and visualization
Xia, J., & Wishart, D. S. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq418 · Cited by 767 · see citing works
Reconstituted NALP1 Inflammasome Reveals Two-Step Mechanism of Caspase-1 Activation
Faustin, B., Lartigue, L., Bruey, J., Luciano, F., Sergienko, E. A., Bailly‐Maitre, B., Volkmann, N., Hanein, D., Rouiller, I., & Reed, J. C. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.01.032 · Cited by 709 · see citing works
Self-citationNwankwo, T., Yoon, S. S., Burt, V. L., & Gu, Q. (2013) · PubMed · Cited by 691 · see citing works
Furman, D., Hejblum, B. P., Simon, N., Jojic, V., Dekker, C. L., Thiébaut, R., Tibshirani, R. J., & Davis, M. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321060111 · Cited by 678 · see citing works
Self-citationCanonical Nlrp3 Inflammasome Links Systemic Low-Grade Inflammation to Functional Decline in Aging
Youm, Y.-H., Grant, R. W., McCabe, L. R., Albarado, D. C., Nguyen, K. Y., Ravussin, A., Pistell, P., Newman, S., Carter, R., Laque, A., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.010 · Cited by 674 · see citing works
Inflammasomes in carcinogenesis and anticancer immune responses
Zitvogel, L., Kepp, O., Galluzzi, L., & Kroemer, G. (2012) · Nature Immunology · doi:10.1038/ni.2224 · Cited by 593 · see citing works
tRNA cleavage is a conserved response to oxidative stress in eukaryotes
Thompson, D. M., Lu, C. C., Green, P. J., & Parker, R. (2008) · RNA · doi:10.1261/rna.1232808 · Cited by 570 · see citing works
DC isoketal-modified proteins activate T cells and promote hypertension
Kirabo, A., Fontana, V., de Faria, A. P., Loperena, R., Galindo, C. L., Wu, J., Bikineyeva, A. T., Dikalov, S., Xiao, L., Chen, W., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74084 · Cited by 539 · see citing works
Effects of Severe Hypertension on Endothelial and Platelet Microparticles
Preston, R. A., Jy, W., Jimenez, J. J., Mauro, L. M., Horstman, L. L., Valle, M., Aime, G., & Ahn, Y. S. (2003) · Hypertension · doi:10.1161/01.hyp.0000049760.15764.2d · Cited by 499 · see citing works
Evolution of Inflammatory Diseases
Okin, D. A., & Medzhitov, R. M. (2012) · Current Biology · doi:10.1016/j.cub.2012.07.029 · Cited by 390 · see citing works
Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation
Hottz, E. D., Lopes, J. F., Freitas, C., Valls-de-Souza, R., Oliveira, M. F., Bozza, M. T., Da Poian, A. T., Weyrich, A. S., Zimmerman, G. A., Bozza, F. A., et al. (2013) · Blood · doi:10.1182/blood-2013-05-504449 · Cited by 348 · see citing works
Inflammation as “common soil” of the multifactorial diseases
Scrivo, R., Vasile, M., Bartosiewicz, I., & Valesini, G. (2010) · Autoimmunity Reviews · doi:10.1016/j.autrev.2010.12.006 · Cited by 337 · see citing works
Arai, Y., Martin-Ruiz, C. M., Takayama, M., Abe, Y., Takebayashi, T., Koyasu, S., Suematsu, M., Hirose, N., & von Zglinicki, T. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.07.029 · Cited by 333 · see citing works
Cytomegalovirus infection enhances the immune response to influenza
Furman, D., Jojic, V., Sharma, S., Shen-Orr, S. S., L. Angel, C. J., Onengut-Gumuscu, S., Kidd, B. A., Maecker, H. T., Concannon, P., Dekker, C. L., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa2293 · Cited by 332 · see citing works
Self-citationPreactivated Peripheral Blood Monocytes in Patients With Essential Hypertension
Dörffel, Y., Lätsch, C., Stuhlmüller, B., Schreiber, S., Scholze, S., Burmester, G. R., & Scholze, J. (1999) · Hypertension · doi:10.1161/01.hyp.34.1.113 · Cited by 265 · see citing works
Yaari, G., Bolen, C. R., Thakar, J., & Kleinstein, S. H. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt660 · Cited by 262 · see citing works
Self-citationInflammation and Cardiovascular Disease
Fearon, W. F., & Fearon, D. T. (2008) · Circulation · doi:10.1161/circulationaha.108.772491 · Cited by 241 · see citing works
The role of inflammation in age-related disease
Howcroft, T. K., Campisi, J., Louis, G. B., Smith, M. T., Wise, B., Wyss-Coray, T., Augustine, A. D., McElhaney, J. E., Kohanski, R., & Sierra, F. (2013) · Aging · doi:10.18632/aging.100531 · Cited by 239 · see citing works
Crippa, A., Discacciati, A., Larsson, S. C., Wolk, A., & Orsini, N. (2014) · American Journal of Epidemiology · doi:10.1093/aje/kwu194 · Cited by 191 · see citing works
Zhang, C., Boini, K. M., Xia, M., Abais, J. M., Li, X., Liu, Q., & Li, P. (2012) · Hypertension · doi:10.1161/hypertensionaha.111.189688 · Cited by 185 · see citing works
Apoptosis and other immune biomarkers predict influenza vaccine responsiveness
Furman, D., Jojic, V., Kidd, B., Shen‐Orr, S., Price, J., Jarrell, J., Tse, T., Huang, H., Lund, P., Maecker, H. T., et al. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.15 · Cited by 184 · see citing works
Self-citationEffects of Aging, Cytomegalovirus Infection, and EBV Infection on Human B Cell Repertoires
Wang, C., Liu, Y., Xu, L. T., Jackson, K., Roskin, K. M., Pham, T. D., Laserson, J., Marshall, E. L., Seo, K., Lee, J.-Y., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301384 · Cited by 179 · see citing works
Self-citationAlzheimer's disease, autoimmunity and inflammation. The good, the bad and the ugly
Sardi, F., Fassina, L., Venturini, L., Inguscio, M., Guerriero, F., Rolfo, E., & Ricevuti, G. (2011) · Autoimmunity Reviews · doi:10.1016/j.autrev.2011.09.005 · Cited by 171 · see citing works
Systemic Inflammation Predicts All-Cause Mortality: A Glasgow Inflammation Outcome Study
Proctor, M. J., McMillan, D. C., Horgan, P. G., Fletcher, C. D., Talwar, D., & Morrison, D. S. (2015) · PLOS ONE · doi:10.1371/journal.pone.0116206 · Cited by 168 · see citing works
Lelo, A., Miners, J. O., Robson, R. A., & Birkett, D. (1986) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1986.10 · Cited by 159 · see citing works
NLRC5 Deficiency Selectively Impairs MHC Class I- Dependent Lymphocyte Killing by Cytotoxic T Cells
Staehli, F., Ludigs, K., Heinz, L. X., Seguín-Estévez, Q., Ferrero, I., Braun, M., Schroder, K., Rebsamen, M., Tardivel, A., Mattmann, C., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102671 · Cited by 154 · see citing works
Shen-Orr, S. S., Furman, D., Kidd, B. A., Hadad, F., Lovelace, P., Huang, Y.-W., Rosenberg-Hasson, Y., Mackey, S., Grisar, F. A. G., Pickman, Y., et al. (2016) · Cell Systems · doi:10.1016/j.cels.2016.09.009 · Cited by 154 · see citing works
Self-citationOuyang, X., Ghani, A., Malik, A. F., Wilder, T., Colegio, O. R., Flavell, R. A., Cronstein, B. N., & Mehal, W. Z. (2013) · Nature Communications · doi:10.1038/ncomms3909 · Cited by 129 · see citing works
NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo
Rauch, I., Tenthorey, J. L., Doyle, R. N., Moussawi, K. A., Kang, J. J., Kang, C., Kazmierczak, B. I., & Vance, R. E. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20151809 · Cited by 109 · see citing works
Determinants of Platelet Activation in Human Essential Hypertension
Minuz, P., Patrignani, P., Gaino, S., Seta, F., Capone, M. L., Tacconelli, S., Degan, M., Faccini, G., Fornasiero, A., Talamini, G., et al. (2003) · Hypertension · doi:10.1161/01.hyp.0000105109.44620.1b · Cited by 90 · see citing works
Omi, T., Kumada, M., Kamesaki, T., Okuda, H., Munkhtulga, L., Yanagisawa, Y., Utsumi, N., Gotoh, T., Hata, A., Soma, M., et al. (2006) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201698 · Cited by 86 · see citing works
Platelet Activation in Essential Hypertension: Implications for Antiplatelet Treatment
Gkaliagkousi, Ε., Passacquale, G., Δούμα, Σ., Zamboulis, C., & Ferro, A. (2010) · American Journal of Hypertension · doi:10.1038/ajh.2009.247 · Cited by 80 · see citing works
RNA metabolism in uremic patients: Accumulation of modified ribonucleosides in uremic serum
Niwa, T., Takeda, N., & Yoshizumi, H. (1998) · Kidney International · doi:10.1046/j.1523-1755.1998.00944.x · Cited by 76 · see citing works
A modified generalized Fisher method for combining probabilities from dependent tests
Dai, H. D., Leeder, J. S., & Cui, Y. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00032 · Cited by 68 · see citing works
The Expression Changes of Inflammasomes in the Aging Rat Kidneys
Song, F., Ma, Y., Bai, X., & Chen, X. (2015) · The Journals of Gerontology Series A · doi:10.1093/gerona/glv078 · Cited by 35 · see citing works
Johansson, Å., Eriksson, N., Becker, R. C., Storey, R. F., Himmelmänn, A., Hagström, E., Varenhorst, C., Axelsson, T., Barratt, B. J., James, S. K., et al. (2015) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.114.000724 · Cited by 29 · see citing works
Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels
Zeller, T., Haase, T., Müller, C., Riess, H., Lau, D., Zeller, S., Krause, J., Baumert, J. J., Pleß, O., Dupuis, J., et al. (2015) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.115.001079 · Cited by 23 · see citing works
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Sorted by citations
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., Fonseca, F., Nicolau, J., Koenig, W., Anker, S. D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1707914 · Cited by 9,482 · see citing works
Chronic inflammation in the etiology of disease across the life span
Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., Ferrucci, L., Gilroy, D. W., Fasano, A., Miller, G. W., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0675-0 · Cited by 4,915 · see citing works
Self-citationInflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443 · see citing works
“At the same time, inflammation promotes oxidation through inflammatory mediators.(205,206) Based on the close relationship among oxidative stress, inflammation, and aging, Dela Fuente et al.”
BackgroundWhy does COVID-19 disproportionately affect older people?
Mueller, A. L., McNamara, M. S., & Sinclair, D. A. (2020) · Aging · doi:10.18632/aging.103344 · Cited by 1,128 · see citing works
Sayed, N., Huang, Y., Nguyen, K., Krejciova-Rajaniemi, Z., Grawe, A. P., Gao, T., Tibshirani, R., Hastie, T., Alpert, A., Cui, L., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00082-y · Cited by 572 · see citing works
Self-citationA clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring
Alpert, A., Pickman, Y., Leipold, M., Rosenberg-Hasson, Y., Ji, X., Gaujoux, R., Rabani, H., Starosvetsky, E., Kveler, K., Schaffert, S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0381-y · Cited by 513 · see citing works
Self-citationSkin barrier immunity and ageing
Chambers, E. S., & Vukmanovic‐Stejic, M. (2019) · Immunology · doi:10.1111/imm.13152 · Cited by 505 · see citing works
“Inflamm-ageing is known to negatively impact on immunity as in older people who had 331 elevated IL-1β they had increased risk of morbidity and mortality (105).”
BackgroundNutrition, inflammation and cancer
Zitvogel, L., Pietrocola, F., & Kroemer, G. (2017) · Nature Immunology · doi:10.1038/ni.3754 · Cited by 446 · see citing works
Cai, Y., Song, W., Li, J., Jing, Y., Liang, C., Zhang, L., Zhang, X., Zhang, W., Liu, B., An, Y., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-022-2161-3 · Cited by 436 · see citing works
Clonal haematopoiesis: connecting ageing and inflammation in cardiovascular disease
Jaiswal, S., & Libby, P. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0247-5 · Cited by 386 · see citing works
The role of mitochondria in aging
Jang, J. Y., Blum, A., Liu, J., & Finkel, T. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120842 · Cited by 358 · see citing works
“Besides evidence for augmented basal cytokine signaling, chronic activation of the inflammasome with elevated IL-1β levels appears to identify a subset of elderly individuals with higher rates of essential hypertension, arterial stiffness, and all-cause mortality (15).”
Calabrese, V., Santoro, A., Monti, D., Crupi, R., Di Paola, R., Latteri, S., Cuzzocrea, S., Zappia, M., Giordano, J., Calabrese, E. J., et al. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.10.379 · Cited by 356 · see citing works
“In individuals over 85 years of age, the elevated expression of inflammasome gene modules is associated with all-cause mortality [125].”
BackgroundElyahu, Y., Hekselman, I., Eizenberg-Magar, I., Berner, O., Strominger, I., Schiller, M., Mittal, K., Nemirovsky, A., Eremenko, E., Vital, A., et al. (2019) · Science Advances · doi:10.1126/sciadv.aaw8330 · Cited by 324 · see citing works
Immune and inflammatory mechanisms in hypertension
Guzik, T. J., Nosalski, R., Maffia, P., & Drummond, G. R. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00964-1 · Cited by 346 · see citing works
“The analysis of expression profiles of a gene module related to inflammasome activity enabled the stratification of older individuals into two distinct groups 249 .”
The role of inflammasomes in kidney disease
Komada, T., & Muruve, D. A. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0158-z · Cited by 311 · see citing works
Pathological mechanisms and therapeutic outlooks for arthrofibrosis
Usher, K. M., Zhu, S., Mavropalias, G., Carrino, J. A., Zhao, J., & Xu, J. (2019) · Bone Research · doi:10.1038/s41413-019-0047-x · Cited by 291 · see citing works
The impact of ageing on monocytes and macrophages
De Maeyer, R. P. H., & Chambers, E. S. (2021) · Immunology Letters · doi:10.1016/j.imlet.2020.12.003 · Cited by 275 · see citing works
Systems immunology: just getting started
Davis, M. M., Tato, C. M., & Furman, D. (2017) · Nature Immunology · doi:10.1038/ni.3768 · Cited by 273 · see citing works
Self-citationAutophagy in Cardiovascular Aging
Abdellatif, M., Sedej, S., Carmona-Gutierrez, D., Madeo, F., & Kroemer, G. (2018) · Circulation Research · doi:10.1161/circresaha.118.312208 · Cited by 239 · see citing works
“SRT1720 but also for other autophagy inducers like metformin(210) and caffeine,(211,212) which reportedly retard cardiac aging.(105,213,214) Similarly, other candidate autophagy inducers(215)”
BackgroundJin, G., Xu, M., Zou, M., & Duan, S. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.01.037 · Cited by 236 · see citing works
“ac4C and Metabolic Diseases Furman et al.(63) found that increasing ac4C and adenine levels in rats correlated with hypertensiveness in rats.”
BackgroundInfluentialInflammasomes as therapeutic targets in human diseases
Li, Y., Huang, H., Liu, B., Zhang, Y. L., Pan, X., Yu, X., Shen, Z., & Song, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00650-z · Cited by 235 · see citing works
“Interestingly, caffeine was shown to inhibit the metabolite-induced IL-1β production.(66,67) NLRP3 inflammasome also plays an important role in the development of atrial fibrillation (AF).”
BackgroundPeripheral immune system in aging and Alzheimer’s disease
Cao, W., & Zheng, H. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0284-2 · Cited by 214 · see citing works
“The expression of specific inflammasome gene modules in older individuals is associated with higher incidence of elevated blood pressure, arterial stiffness, metabolic dysfunction, oxidative stress and shortened life span [21].”
BackgroundMitchell, C. A., Verovskaya, E. V., Calero‐Nieto, F. J., Olson, O. C., Swann, J. W., Wang, X., Hérault, A., Dellorusso, P. V., Zhang, S. Y., Svendsen, A. F., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-022-01053-0 · Cited by 219 · see citing works
Inflammaging: Implications in Sarcopenia
Antuña, E., Cachán-Vega, C., Bermejo-Millo, J. C., Potes, Y., Caballero, B., Vega‐Naredo, I., Coto‐Montes, A. M., & García-González, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315039 · Cited by 223 · see citing works
The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging
Meyers, A. K., & Zhu, X. (2020) · Cells · doi:10.3390/cells9081808 · Cited by 203 · see citing works
“The former group was associated with measures of all-cause mortality, again supporting the concept that targeting inflammasome components may ameliorate chronic inflammation and various other age-associated conditions [141].”
BackgroundAwad, F., Assrawi, E., Jumeau, C., Georgin-Lavialle, S., Cobret, L., Duquesnoy, P., Piterboth, W., Thomas, L., Stankovic-Stojanovic, K., Louvrier, C., et al. (2017) · PLOS ONE · doi:10.1371/journal.pone.0175336 · Cited by 191 · see citing works
“Recent work has shown that elevated and persistent expression of inflammasome genes in older individuals is associated with all causes of mortality [60].”
Jin, W.-N., Shi, K., He, W., Sun, J.-H., Van Kaer, L., Shi, F.-D., & Liu, Q. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00745-w · Cited by 179 · see citing works
Molecular mechanisms of inflammasome signaling
Mathur, A., Hayward, J. A., & Man, S. M. (2017) · Journal of Leukocyte Biology · doi:10.1189/jlb.3mr0617-250r · Cited by 189 · see citing works
Aging and InflammationPreprint
Singh, A., Schurman, S. H., Bektas, A., Kaileh, M., Roy, R., Wilson, D. M., Sen, R., & Ferrucci, L. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041197 · Cited by 194 · see citing works
Targeting Inflammation and Immunosenescence to Improve Vaccine Responses in the Elderly
Pereira, B. I., Xu, X., & Akbar, A. N. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.583019 · Cited by 182 · see citing works
“A common feature among these groups is the presence of a chronic inflammatory background that has been associated with adverse health outcomes (170).”
BackgroundThe role of inflammasomes in vascular cognitive impairment
Poh, L., Sim, W. L., Jo, D., Dinh, Q. N., Drummond, G. R., Sobey, C. G., Chen, C., Lai, M. K. P., Fann, D. Y., & Arumugam, T. V. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00506-8 · Cited by 167 · see citing works
“Nucleotidederived metabolites, including adenine and N4acetylcytidine (N4A), can both prime and activate the NAIP-NLRC4 inflammasome [254], and could be relevant given that oxidative DNA damage has been described in VCI patients [60].”
BackgroundThe Aging Risk and Atherosclerosis: A Fresh Look at Arterial Homeostasis
Head, T., Daunert, S., & Goldschmidt‐Clermont, P. J. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00216 · Cited by 165 · see citing works
“IL-1β is also activated via inflammasomes containing NOD-like receptors (NLRs; Furman et al., 2017; Ridker et al., 2017).”
BackgroundInternational Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update
IJzerman, A. P., Jacobson, K. A., Müller, C. E., Cronstein, B. N., & Cunha, R. A. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.121.000445 · Cited by 163 · see citing works
“Indeed, the alteration of purinergic metabolism seems to be a prominent characteristic—a metabolic fingerprint of the aging process in different organisms (Furman et al., 2017; Gao et al., 2018a).”
Aging drives <i>Tet2</i> <i>+/−</i> clonal hematopoiesis via IL-1 signaling
Caiado, F., Kovtonyuk, L. V., Gonullu, N. G., Fullin, J., Boettcher, S., & Manz, M. G. (2023) · Blood · doi:10.1182/blood.2022016835 · Cited by 161 · see citing works
NLRP3 inflammasome activation in inflammaging
Latz, E., & Duewell, P. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.09.001 · Cited by 174 · see citing works
Vallania, F., Tam, A., Lofgren, S., Schaffert, S. A., Azad, T. D., Bongen, E., Haynes, W. A., Alsup, M., Alonso, M. N., Davis, M. M., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07242-6 · Cited by 158 · see citing works
Self-citationDisease tolerance: concept and mechanisms
McCarville, J. L., & Ayres, J. S. (2017) · Current Opinion in Immunology · doi:10.1016/j.coi.2017.12.003 · Cited by 149 · see citing works
Mav, D., Shah, R., Howard, B. E., Auerbach, S. S., Bushel, P. R., Collins, J. B., Gerhold, D. L., Judson, R., Karmaus, A. L., Maull, E. A., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0191105 · Cited by 156 · see citing works
Role of Dendritic Cells in Inflammation and Loss of Tolerance in the Elderly
Agrawal, A., Agrawal, S., & Gupta, S. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00896 · Cited by 154 · see citing works
“A recent study (66) in humans has demonstrated a direct correlation between specific inflammasome expression”
BackgroundExercise suppresses neuroinflammation for alleviating Alzheimer’s disease
Wang, M., Zhang, H., Liang, J., Huang, J., & Chen, N. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02753-6 · Cited by 149 · see citing works
Extracellular nucleosides and nucleotides as immunomodulators
Kepp, O., Loos, F., Liu, P., & Kroemer, G. (2017) · Immunological Reviews · doi:10.1111/imr.12571 · Cited by 144 · see citing works
Neutrophils in aging and aging‐related pathologies
Avondt, K. V., Strecker, J., Tulotta, C., Minnerup, J., Schulz, C., & Soehnlein, O. (2022) · Immunological Reviews · doi:10.1111/imr.13153 · Cited by 146 · see citing works
Lannes, N., Eppler, E., Etemad, S., Yotovski, P., & Filgueira, L. (2017) · Oncotarget · doi:10.18632/oncotarget.23106 · Cited by 139 · see citing works
“Aging goes in parallel with systemic chronic activation of the immune system and polarization towards a low-level inflammatory status [266, 267].”
BackgroundHorn, S. R., Long, M. M., Nelson, B. W., Allen, N. B., Fisher, P. A., & Byrne, M. L. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.06.016 · Cited by 129 · see citing works
Activation of NLRP3 Inflammasome and Onset of Alzheimer’s Disease
Bai, H., & Zhang, Q. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.701282 · Cited by 129 · see citing works
“It has been found that high expression of NLRP3 and caspase-1 genes was conducive to the formation of aging lesions in the brains of amyloid precursor protein/presenilin-1 (APP/PS-1) transgenic mice (45).”
BackgroundImmunology of the ageing kidney
Sato, Y., & Yanagita, M. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0185-9 · Cited by 126 · see citing works
Pathophysiology of Acute Myeloid Leukemia
Wachter, F., & Pikman, Y. (2024) · Acta Haematologica · doi:10.1159/000536152 · Cited by 131 · see citing works
“Aging itself has been associated with chronic in fl ammation [17].”
BackgroundSato, Y., Boor, P., Fukuma, S., Klinkhammer, B. M., Haga, H., Ogawa, O., Floege, J., & Yanagita, M. (2020) · Kidney International · doi:10.1016/j.kint.2020.02.023 · Cited by 119 · see citing works
Revisiting the Hallmarks of Aging to Identify Markers of Biological Age
Guerville, F., Barreto, P. D. S., Ader, I., Andrieu, S., Casteilla, L., Dray, C., Fazilleau, N., Guyonnet, S., Langin, D., Liblau, R., et al. (2020) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2019.50 · Cited by 120 · see citing works
“In participants of the Stanford-Ellison cohort aged 60 to >90 yo, inflammasome activation (measured by nlcrc4 and nlrc5 genes expression in whole blood cells and interleukin-1β production) was positively associated with hypertension and arterial stiffness and negatively associated with personal and familial longevity…”
BackgroundAdenosine A2A receptor antagonists: from caffeine to selective non‐xanthines
Jacobson, K. A., Gao, Z., Matricon, P. G., Eddy, M. T., & Carlsson, J. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15103 · Cited by 115 · see citing works
“There are contradictory reports indicating either salutary or harmful effects of human caffeine consumption in inflammatory states, or in combination with drugs, such as the adenosine-boosting drug methotrexate for rheumatoid arthritis (Furman et al., 2017; Malaviya, 2017).”
BackgroundAdipose tissue inflammation in aging
Mau, T., & Yung, R. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.014 · Cited by 110 · see citing works
“While sources of inflammaging remain under investigation, some prominent conversations include immunosenescence 6,11 , self-debris 12 , senescent cells 13 , mitochondria dysfunction 14,15 , microbiome 16 , and adipose tissue 17–20 .”
BackgroundImmunometabolism and HIV-1 pathogenesis: food for thought
Sáez‐Cirión, A., & Sereti, I. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-0381-7 · Cited by 104 · see citing works
The intra‐ and extracellular functions of ASC specks
Franklin, B. S., Latz, E., & Schmidt, F. I. (2017) · Immunological Reviews · doi:10.1111/imr.12611 · Cited by 107 · see citing works
Shen, Y., Malik, S. A., Amir, M., Kumar, P., Cingolani, F., Wen, J., Liu, Y., Zhao, E., Farris, A. B., Raeman, R., et al. (2020) · Hepatology · doi:10.1002/hep.31209 · Cited by 106 · see citing works
“Delineating the mechanisms of IL-1β’s toxic and inflammatory effects is essential to understanding not only the molecular basis of hepatic injury, but also the mechanisms of many other human diseases that have been linked to this cytokine.(11) Macroautophagy (hereafter referred to as autophagy) performs multiple funct…”
BackgroundVukmanovic-Stejic, M., Chambers, E. S., Suárez-Fariñas, M., Sandhu, D., Fuentes-Duculan, J., Patel, N., Agius, E., Lacy, K. E., Turner, C. T., Larbi, A., et al. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.10.032 · Cited by 103 · see citing works
“Previous studies demonstrated that systemic inflammation, as indicated by increased levels of serum IL-6, TNF-a, and C-reactive protein (CRP), are strong predictors for frailty and mortality during aging.(12,13) Ingenuity Pathway Analysis indicated a significant association between the inflammatory gene in the skin of…”
Shokoples, B. G., Paradis, P., & Schiffrin, E. L. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.315116 · Cited by 102 · see citing works
CD73-derived adenosine controls inflammation and neurodegeneration by modulating dopamine signalling
Meng, F. J., Guo, Z., Hu, Y., Mai, W., Zhang, Z., Zhang, B., Ge, Q., Lou, H., Guo, F., Chen, J., et al. (2018) · Brain · doi:10.1093/brain/awy351 · Cited by 98 · see citing works
Emerging Role of the Inflammasome and Pyroptosis in Hypertension
Miguel, C. D., Pelegrı́n, P., Baroja‐Mazo, A., & Cuevas, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031064 · Cited by 100 · see citing works
“Other inflammasomes, such as the NLRC4 inflammasome, have been tentatively implicated in blood pressure regulation in mice [137]; however, further studies are needed to confirm this involvement.”
BackgroundPaiva, C., Beserra, B. T. S., Reis, C., Dórea, J. G., Costa, T. D., & Amato, A. A. (2017) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2017.1386159 · Cited by 99 · see citing works
“Recently, Furman et al (2017) reported that higher caffeine consumption was associated with reduced inflammasome activation in humans and that treatment of human macrophages with caffeine at concentrations similar to those found in the plasma of coffee consumers inhibited IL-1beta secretion (Furman…”
BackgroundCardiovascular Aging and Longevity
Pietri, P. G., & Stefanadis, C. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.11.023 · Cited by 99 · see citing works
Impact of COVID-19 on Mitochondrial-Based Immunity in Aging and Age-Related Diseases
Ganji, R., & Reddy, P. H. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.614650 · Cited by 96 · see citing works
Systems biology of personalized nutrition
van Ommen, B., van den Broek, T., de Hoogh, I. M., van Erk, M., van Someren, E. P., Rankouhi, T. R., Anthony, J. C., Hogenelst, K., Pasman, W. J., Boorsma, A., et al. (2017) · Nutrition Reviews · doi:10.1093/nutrit/nux029 · Cited by 95 · see citing works
“Many processes involved in aging and increased frailty (energy/glucose/insulin homeostasis, protein homeostasis, redox homeostasis, mitochondrial homeostasis, stress resistance, inflammation control) are part of the systems flexibility concept.(26,27)”
Chambers, E. S., Vukmanovic-Stejic, M., Shih, B. B., Trahair, H., Subramanian, P., Devine, O. P., Glanville, J., Gilroy, D., Rustin, M. H. A., Freeman, T. C., et al. (2021) · Nature Aging · doi:10.1038/s43587-020-00010-6 · Cited by 96 · see citing works
Can blocking inflammation enhance immunity during aging?
Chambers, E. S., & Akbar, A. N. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.03.016 · Cited by 92 · see citing works
“In addition to elevated IL-6, CRP and TNFα, IL-1β and inflammasome related genes are also good predictors of all-cause mortality (13).”
BackgroundWhat Is the Role of the Inflammation in the Pathogenesis of Heart Failure?
Castillo, E. C., Vázquez‐Garza, E., Yee-Trejo, D., García‐Rivas, G., & Torre‐Amione, G. (2020) · Current Cardiology Reports · doi:10.1007/s11886-020-01382-2 · Cited by 92 · see citing works
NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation
Shi, J., Yang, C., Zhang, J., Zhao, K., Li, P., Kong, C., Wu, X., Sun, H., Zheng, R., Sun, W. Y., et al. (2023) · Circulation Research · doi:10.1161/circresaha.122.322244 · Cited by 93 · see citing works
“9 13 However, the role of ac4C acetylations in cardiac remodeling remains unclear.”
BackgroundElyahu, Y., & Monsonego, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101231 · Cited by 91 · see citing works
“, 2020), a self-renewal subset that supports long immunological memory (Gattinoni et al., 2011).”
BackgroundEffect and Regulation of the NLRP3 Inflammasome During Renal Fibrosis
Zhang, H., & Wang, Z. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00379 · Cited by 87 · see citing works
“Age-associated renal diseases are related to the NLRC4 inflammasome (Furman et al., 2017).”
BackgroundSystems Immunology: Learning the Rules of the Immune System
Villani, A., Sarkizova, S., & Hacohen, N. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053035 · Cited by 84 · see citing works
“…immune responses to vaccines, or viral and bacterial infections (8−17), progression to active disease in tuberculosis (18, 19), severity of autoimmune diseases such as systemic lupus erythematosus (SLE) (20–23), as well as immune responses as a function of age, genetics, and environment (24–27).”
BackgroundActivation and Function of NLRP3 Inflammasome in Bone and Joint-Related Diseases
Murakami, T., Nakaminami, Y., Takahata, Y., Hata, K., & Nishimura, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105365 · Cited by 87 · see citing works
“Indeed, inflammasome modules have correlated with health and longevity in some cohorts [177].”
BackgroundZaghlool, S. B., Kühnel, B., Elhadad, M. A., Kader, S. A., Halama, A., Thareja, G., Engelke, R., Sarwath, H., Al‐Dous, E., Mohamoud, Y. A., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13831-w · Cited by 83 · see citing works
Yan, Q., Zhou, J., Wang, Z., Ding, X., Ma, X., Wan, L., Jia, X., Gao, S., & Lu, C. (2023) · Nature Communications · doi:10.1038/s41467-023-42135-3 · Cited by 81 · see citing works
“It should be noted that N 4 -acetylcytidine, as a nucleoside metabolite itself, induces the activation of the in fl ammasome in microglia or THP-1 cells 51,52 .”
Kang, Y., Zhang, H., Zhao, Y., Wang, Y., Wang, W. T., He, Y., Zhang, W. K., Zhang, W., Zhu, X., Zhou, Y., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.071 · Cited by 81 · see citing works
Genetic regulation of gene expression and splicing during a 10-year period of human aging
Balliu, B., Durrant, M. G., de Goede, O. M., Abell, N. S., Li, X., Liu, B., Gloudemans, M. J., Cook, N. L., Smith, K. S., Knowles, D. A., et al. (2019) · Genome biology · doi:10.1186/s13059-019-1840-y · Cited by 83 · see citing works
Coffee Consumption and Incident Tachyarrhythmias
Kim, E., Hoffmann, T. J., Nah, G., Vittinghoff, E., Delling, F. N., & Marcus, G. M. (2021) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2021.3616 · Cited by 81 · see citing works
Kveler, K., Starosvetsky, E., Ziv-Kenet, A., Kalugny, Y., Gorelik, Y., Shalev-Malul, G., Aizenbud-Reshef, N., Dubovik, T., Briller, M., Campbell, J. P., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4152 · Cited by 74 · see citing works
“Moreover, elevated RETN directly induces IL6 secretion 41 , contributing to the constant low-grade inflammatory state associated with age and cardio-vascular conditions 42,43 .”
Fibronectin type III domain‐containing 5 improves aging‐related cardiac dysfunction in mice
Hu, C., Zhang, X., Hu, M., Teng, T., Yuan, Y., Song, P. K., Kong, C., Xu, S., Ma, Z., & Tang, Q. (2022) · Aging Cell · doi:10.1111/acel.13556 · Cited by 78 · see citing works
“Various inflammatory biomarkers, including IL- 6 and TNF- α, are identified as predictors of many aging phenotypes (e.g., energy metabolism, immune senescence, and muscle degeneration) (Furman et al., 2017).”
BackgroundATP release drives heightened immune responses associated with hypertension
Zhao, T. V., Yu, L., Liu, X., Xia, S., Shi, P. D., Li, L., Chen, Z., Yin, C., Eriguchi, M., Chen, Y., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aau6426 · Cited by 77 · see citing works
Pan, Y., Long, X., Yi, R., & Zhao, X. (2018) · Nutrients · doi:10.3390/nu10091280 · Cited by 76 · see citing works
“Animal model studies Nutrients 2018, 10, 1280 13 of 17 showed that caffeine could also inhibit acute alcoholic liver injury possibly by imparting antioxidant effects and inhibiting the expressions of IL-1β and TNF-α [60].”
BackgroundInfluentialMitochondria: multifaceted regulators of aging
Son, J. M., & Lee, C. D. (2019) · BMB Reports · doi:10.5483/bmbrep.2019.52.1.300 · Cited by 76 · see citing works
“development of age-related diseases (92, 93).”
Inflammation-Accelerated Senescence and the Cardiovascular System: Mechanisms and Perspectives
Pinto, R. D., & Ferri, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123701 · Cited by 75 · see citing works
“Inflammasome hyperactivation was described in the peripheral blood of older human donors with hypertension, as a potential contributing mechanism to age-associated inflammation and hypertension [49].”
BackgroundSuryavanshi, S. V., Zaiachuk, M., Pryimak, N., Kovalchuk, I., & Kovalchuk, O. (2022) · Cells · doi:10.3390/cells11091391 · Cited by 75 · see citing works
“NLRP3 inflammasome activation via DAMPs and oxidative stress has been implicated in increasing susceptibility to chronic inflammatory disorders, such as cardiovascular diseases [44,47].”
BackgroundSharma, B., Satija, G., Madan, A., Garg, M., Alam, M. M., Shaquiquzzaman, M., Khanna, S. M., Tiwari, P., Parvez, S., Iqubal, A., et al. (2022) · Inflammation · doi:10.1007/s10753-022-01730-0 · Cited by 65 · see citing works
ENaC in Salt-Sensitive Hypertension: Kidney and Beyond
Pitzer, A. L., Beusecum, J. P. V., Kleyman, T. R., & Kirabo, A. (2020) · Current Hypertension Reports · doi:10.1007/s11906-020-01067-9 · Cited by 74 · see citing works
Wang, F., Tessier, A., Liang, L., Wittenbecher, C., Haslam, D. E., Fernández-Duval, G., Eliassen, A. H., Rexrode, K. M., Tobias, D. K., Li, J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41515-z · Cited by 74 · see citing works
Goh, G., Ahn, M., Zhu, F., Lee, L. B., Luo, D., Irving, A. T., & Wang, L. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003352117 · Cited by 71 · see citing works
Hyperglycemia-induced inflamm-aging accelerates gingival senescence via NLRC4 phosphorylation
Zhang, P., Wang, Q., Nie, L., Zhou, X., Zhou, X., Zhao, P., Ji, N., Liang, X., Ding, Y., Yuan, Q., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.010648 · Cited by 74 · see citing works
“NLRC4 may be a key factor in the regulation of inflammaging (18, 19, 22, 24), and IRF8 is required for activation of NLRC4 inflammasome (26).”
BackgroundFlavonoids: Broad Spectrum Agents on Chronic Inflammation
Lim, H. A., Heo, M. Y., & Kim, H. P. (2019) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2019.034 · Cited by 71 · see citing works
“Expression of inflammasome gene modules including IL-1β is positively associated with human aging, especially in those aged over 85 years (Furman et al., 2017).”
BackgroundCANTOS Trial Validates the Inflammatory Pathogenesis of Atherosclerosis
Weber, C., & von Hundelshausen, P. (2017) · Circulation Research · doi:10.1161/circresaha.117.311984 · Cited by 70 · see citing works
“Moreover, the expression of specific inflammasome gene modules affecting IL-1β, CXCL1, and CXCL12 has been associated with death from any cause, hypertension and higher arterial stiffness in elderly patients.(13) These findings may prompt considerations toward exploiting alternative inflammatory targets.”
BackgroundSIRT6 in Senescence and Aging-Related Cardiovascular Diseases
Li, X., Liu, L., Li, T. X., Liu, M., Wang, Y., Ma, H., Mu, N., & Wang, H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.641315 · Cited by 73 · see citing works
Involvement of Inflammasome Components in Kidney Disease
Aranda‐Rivera, A. K., Srivastava, A., Cruz‐Gregorio, A., Pedraza‐Chaverrí, J., Mulay, S. R., & Scholze, A. (2022) · Antioxidants · doi:10.3390/antiox11020246 · Cited by 71 · see citing works
Chavakis, T., Wielockx, B., & Hajishengallis, G. (2021) · Annual Review of Physiology · doi:10.1146/annurev-physiol-052521-013627 · Cited by 70 · see citing works
The Role of NLRP3 Inflammasome Activities in Bone Diseases and Vascular Calcification
Yu, C., Zhang, C., Kuang, Z., & Zheng, Q. (2020) · Inflammation · doi:10.1007/s10753-020-01357-z · Cited by 67 · see citing works
Kotyla, P. J., Engelmann, M., Giemza-Stokłosa, J., Wnuk, B. R., & Islam, M. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052449 · Cited by 68 · see citing works
“In addition, a substantial subset of elderly individuals showed inflammasome activation and increased IL-1β levels [64].”
BackgroundRNA modifications in cardiovascular diseases, the potential therapeutic targets
Wu, Y., Zhan, S., Xu, Y., & Gao, X. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119565 · Cited by 67 · see citing works
Similar but different: virtual memory CD8 T cells as a memory‐like cell population
Hussain, T., & Quinn, K. M. (2019) · Immunology and Cell Biology · doi:10.1111/imcb.12277 · Cited by 65 · see citing works
Adam, M. G., Beyer, G., Christiansen, N., Kamlage, B., Pilarsky, C. P., Distler, M., Fahlbusch, T., Chromik, A. M., Klein, F., Bahra, M., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-320723 · Cited by 65 · see citing works
“53 Inflammasome activation, yet not a pancreas specific process, is involved in pancreatic healing and fibrosis.”
Update of inflammasome activation in microglia/macrophage in aging and aging‐related disease
Hu, M., Lin, Y., Zhang, B., Lu, D., Lu, Z., & Cai, W. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13262 · Cited by 65 · see citing works
Hajishengallis, G., Li, X., Divaris, K., & Chavakis, T. (2022) · Periodontology 2000 · doi:10.1111/prd.12421 · Cited by 67 · see citing works
A roadmap towards personalized immunology
Delhalle, S., Bode, S. F. N., Balling, R., Ollert, M. W., & HeFeng, F. Q. (2018) · npj Systems Biology and Applications · doi:10.1038/s41540-017-0045-9 · Cited by 66 · see citing works
“On a molecular level, it has already been demonstrated that the gene modules that were organized based on the transcript expression patterns in the peripheral blood of elderly individuals can also be used to stratify those individuals into two completely different clinical and immunological states.(67) More detailed w…”
- Authors
- Furman, D., Chang, J., Lartigue, L., Bolen, C. R., Haddad, F., Gaudilliere, B., Ganio, E. A., Fragiadakis, G. K., Spitzer, M. H., Douchet, I., Daburon, S., Moreau, J.-F., Nolan, G. P., Blanco, P., Déchanet-Merville, J., Dekker, C. L., Jojic, V., Kuo, C. J., Davis, M. M., & Faustin, B.
- Affiliations
- Sidra Medical and Research Center (QA)
- Stanford Medicine (US)
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- University of North Carolina at Chapel Hill (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Furman, David
- Davis, Mark M
- Faustin, Benjamin
- ORCID
- Venue
- Nature Medicine
- Published
- 2017-01-16
- Volume
- 23
- Issue
- 2
- Pages
- 174-184
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC5320935
- OpenAlex
- W2577141559
- Cited by
- 389
- References
- 53
- Citations by year
- 2026: 13 · 2025: 27 · 2024: 43 · 2023: 47 · 2022: 51 · 2021: 44 · 2020: 52 · 2019: 41 · 2018: 33 · 2017: 37
- FWCI
- 18.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- HAL (submittedVersion, other-oa)
- UNC Libraries
- Funders
- Ellison Medical Foundation
- Fondation pour la Recherche Médicale (DEQ20110421287)
- Ligue Contre le Cancer
- Institut National Du Cancer
- National Institutes of Health (AI090019)
- National Institute of General Medical Sciences (K23GM111657)
- National Institute of Allergy and Infectious Diseases (U19AI090019, U19AI057229)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- inflammasome, IL-1β, NLRC4 inflammasome, aging, chronic inflammation, nucleotide metabolism, adenine, N4-acetylcytidine, oxidative stress, hypertension, arterial stiffness, platelet activation, neutrophils, all-cause mortality, longevity, gene modules
- MeSH terms
- Adenine, Adult, Aged, Aged, 80 and over, Aging, Animals, Blood Platelets, Blood Pressure, Caffeine, Calcium-Binding Proteins, Cell Line, Cytidine, Female, Humans, Hypertension, Inflammation, Macrophages, Male, Middle Aged, Monocytes, Mortality, Neutrophils, Nucleotides, Phenotype, Regression Analysis, Immunoblotting, Platelet Activation, Cytokines, Neutrophil Activation, Oxidative Stress, Intracellular Signaling Peptides and Proteins, Toll-Like Receptor 5, Toll-Like Receptor 8, Toll-Like Receptor 6, Mice, CARD Signaling Adaptor Proteins, Interleukin-1beta, Interleukin 1 Receptor Antagonist Protein, Metabolomics, Young Adult, Inflammasomes, Purinergic P1 Receptor Antagonists, Carotid Intima-Media Thickness, Vascular Stiffness, Transcriptome, Pulse Wave Analysis
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