Drivers of age‐related inflammation and strategies for healthspan extension
Open accessAbstract
Summary: Aging is the greatest risk factor for the development of chronic diseases such as arthritis, type 2 diabetes, cardiovascular disease, kidney disease, Alzheimer's disease, macular degeneration, frailty, and certain forms of cancers. It is widely regarded that chronic inflammation may be a common link in all these age‐related diseases. This raises the question, can one alter the course of aging and potentially slow the development of all chronic diseases by manipulating the mechanisms that cause age‐related inflammation? Emerging evidence suggests that pro‐inflammatory cytokines interleukin‐1 (IL‐1) and IL‐18 show an age‐dependent regulation implicating inflammasome‐mediated caspase‐1 activation in the aging process. The Nod‐like receptor (NLR) family of innate immune cell sensors, such as the nucleotide‐binding domain, leucine‐rich‐containing family, pyrin domain‐containing‐3 (NLRP 3) inflammasome controls the caspase‐1 activation in myeloid‐lineage cells in several organs during aging. The NLRP 3 inflammasome is especially relevant to aging as it can get activated in response to structurally diverse damage‐associated molecular patterns (DAMP s) such as extracellular ATP, excess glucose, ceramides, amyloids, urate, and cholesterol crystals, all of which increase with age. Interestingly, reduction in NLRP 3‐mediated inflammation prevents age‐related insulin resistance, bone loss, cognitive decline, and frailty. NLRP 3 is a major driver of age‐related inflammation and therefore dietary or pharmacological approaches to lower aberrant inflammasome activation holds promise in reducing multiple chronic diseases of age and may enhance healthspan.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Monocytes and tissue-resident macrophages are predominant producers of SASP factors such as IL-1α, IL-1β, IL-6, TNF, and HMGB1.
“Studies have shown that immune cells, including monocytes and tissue-resident macrophages, are the predominant producers of SASP factors such as IL-1α, IL-1β, IL-6, TNF and HMGB1 (refs. 75–78).”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [75]
The “Metabolic disease/T2D” section (page not supplied) credits inflammatory M1 macrophages with increased TNFα, IL-6, and IL-1β in obesity. The “Age-related diseases and inflammation” section says macrophages are major responders to danger signals in aged tissues, but does not establish that monocytes and tissue-resident macrophages are the predominant producers of SASP factors generally, or identify them as producers of IL-1α and HMGB1. (LLM, conf=0.87)
Experimental — accuracy not yet measuredChronic systemic inflammation is associated with aging, is low-grade and persistent, and ultimately causes collateral damage to tissues and organs.
“This type of inflammation is associated with aging and is characterized by being low-grade and persistent, ultimately leading to collateral damage to tissues and organs1,17.”
From An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging (2021) · cites this paper as [17]
Chronic serum hyperuricemia positively correlates with inflammation, DNA damage and OS, and has been implicated in pathogenesis of several disorders, including renal, metabolic, and cardiovascular diseases.
“Accordingly, chronic serum hyperuricemia positively correlates with inflammation, DNA damage and OS, and has been implicated in the pathogenesis of several disorders, including renal, metabolic, and cardiovascular diseases [214,217,218].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [218]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Prevalence of Childhood and Adult Obesity in the United States, 2011-2012
Ogden, C. L., Carroll, M. D., Kit, B. K., & Flegal, K. M. (2014) · JAMA · doi:10.1001/jama.2014.732 · Cited by 8,072 · see citing works
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760 · see citing works
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618 · 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
Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358 · see citing works
Gout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326 · see citing works
Autophagy and Viruses: Adversaries or Allies?
Dong, X., & Levine, B. (2013) · Journal of Innate Immunity · doi:10.1159/000346388 · Cited by 4,441 · 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 · cited 4× · see citing works
“Cholesterol crystals in plaques are one of the important activators of NLRP3 inflammasome and ablation of NLRP3 in mice protects against atherosclerosis (22).”
BackgroundInfluentialChronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
Franceschi, C., & Campisi, J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu057 · Cited by 3,891 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 1× · see citing works
“In a progeroid mouse model of greatly accelerated aging, removal of senescent cells in vivo delayed the aging phenotype in these mice (60).”
BackgroundBauernfeind, F. G., Horvath, G. L., Stutz, A., Alnemri, E. S., MacDonald, K. L., Speert, D. P., Fernandes‐Alnemri, T., Wu, J., Monks, B. G., Fitzgerald, K. A., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901363 · Cited by 3,006 · see citing works
NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.-C., et al. (2013) · Nature · doi:10.1038/nature11729 · Cited by 2,898 · see citing works
Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
Dostert, C., Pétrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., & Tschopp, J. (2008) · Science · doi:10.1126/science.1156995 · Cited by 2,658 · see citing works
The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
Vandanmagsar, B., Youm, Y.-H., Ravussin, A., Galgani, J. E., Stadler, K., Mynatt, R. L., Ravussin, E., Stephens, J. M., & Dixit, V. D. (2011) · Nature Medicine · doi:10.1038/nm.2279 · Cited by 2,655 · see citing works
Self-citationA Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells
Schulz, C., Perdiguero, E. G., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S. E. W., Pollard, J. W., et al. (2012) · Science · doi:10.1126/science.1219179 · Cited by 2,578 · see citing works
The NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441 · see citing works
Hashimoto, D., Chow, A., Noizat, C., Teo, P., Beasley, M. B., Leboeuf, M., Becker, C. D., See, P., Price, J., Lucas, D., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.04.004 · Cited by 2,311 · cited 1× · see citing works
“Tissue-resident macrophages, such as microglia are now generally accepted as yolk sac-derived cells that originate independently of adult hematopoiesis that self-renew by local proliferation (36, 37) and are shaped by their local tissue environment (38).”
BackgroundNishimura, S., Manabe, I., Nagasaki, M., Eto, K., Yamashita, H., Ohsugi, M., Otsu, M., Hara, K., Ueki, K., Sugiura, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.1964 · Cited by 2,230 · see citing works
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease
Youm, Y.-H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., D'Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T. D., et al. (2015) · Nature Medicine · doi:10.1038/nm.3804 · Cited by 2,172 · see citing works
Self-citationMuñoz-Planillo, R., Kuffa, P., Martínez-Colón, G. J., Smith, B. L., Rajendiran, T. M., & Núñez, G. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.016 · Cited by 2,167 · see citing works
Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment
Lavin, Y., Winter, D., Blecher-Gonen, R., David, E., Keren-Shaul, H., Merad, M., Jung, S., & Amit, I. (2014) · Cell · doi:10.1016/j.cell.2014.11.018 · Cited by 2,167 · see citing works
Feuerer, M., Herrero, L., Cipolletta, D., Naaz, A., Wong, J., Nayer, A., Lee, J., Goldfine, A. B., Benoist, C., Shoelson, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.2002 · Cited by 2,145 · see citing works
Davies, L. C., Jenkins, S. J., Allen, J. E., & Taylor, P. R. (2013) · Nature Immunology · doi:10.1038/ni.2705 · Cited by 2,096 · see citing works
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087 · see citing works
Pathogenesis of osteoporosis: concepts, conflicts, and prospects
Raisz, L. G. (2005) · Journal of Clinical Investigation · doi:10.1172/jci27071 · Cited by 1,779 · cited 1× · see citing works
“Decreased bone strength during aging can result from (i) excessive bone resorption or (ii) insufficient bone formation after resorption (64).”
BackgroundSuppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor
Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens, R. D., et al. (2013) · Science · doi:10.1126/science.1227166 · Cited by 1,777 · see citing works
Evans, D. A. (1989) · JAMA · doi:10.1001/jama.262.18.2551 · Cited by 1,627 · see citing works
Normalization of obesity-associated insulin resistance through immunotherapy
Winer, S., Chan, Y., Paltser, G., Truong, D., Tsui, H., Bahrami, J., Dorfman, R., Wang, Y., Zielenski, J., Mastronardi, F., et al. (2009) · Nature Medicine · doi:10.1038/nm.2001 · Cited by 1,370 · see citing works
Shi, C.-S., Shenderov, K., Huang, N.-N., Kabat, J., Abu-Asab, M., Fitzgerald, K. A., Sher, A., & Kehrl, J. H. (2012) · Nature Immunology · doi:10.1038/ni.2215 · Cited by 1,367 · see citing works
Unified Polymerization Mechanism for the Assembly of ASC-Dependent Inflammasomes
Lu, A., Magupalli, V. G., Ruan, J., Yin, Q., Atianand, M. K., Vos, M. R., Schröder, G. F., Fitzgerald, K. A., Wu, H., & Egelman, E. H. (2014) · Cell · doi:10.1016/j.cell.2014.02.008 · Cited by 1,353 · see citing works
Evans, D. A. (1989) · JAMA · doi:10.1001/jama.1989.03430180093036 · Cited by 1,226 · cited 1× · see citing works
“Alzheimer’s disease (AD) is the leading cause of dementia and its single greatest risk factor is age (44).”
BackgroundFat tissue, aging, and cellular senescence
Tchkonia, T., Morbeck, D. E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M. D., & Kirkland, J. L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00608.x · Cited by 1,094 · see citing works
Mechanisms of Disease: is osteoporosis the obesity of bone?
Rosen, C. J., & Bouxsein, M. (2006) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0070 · Cited by 961 · see citing works
The origins of age-related proinflammatory state
Ferrucci, L., Corsi, A., Lauretani, F., Bandinelli, S., Bartali, B., Taub, D. D., Guralnik, J. M., & Longo, D. L. (2005) · Blood · doi:10.1182/blood-2004-07-2599 · Cited by 908 · see citing works
Long-Term Calorie Restriction Is Highly Effective in Reducing the Risk for Atherosclerosis in Humans
Fontana, L., Meyer, T. E., Klein, S., & Holloszy, J. O. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308291101 · Cited by 902 · see citing works
Changes in Bone Mineral Density of the Proximal Femur and Spine with Aging
Riggs, B. L., Wahner, H. W., Seeman, E., Offord, K. P., Dunn, W. L., Mazess, R. B., Johnson, K. A., & Melton, L. J. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110667 · Cited by 816 · see citing works
Yan, Y., Jiang, W., Spinetti, T., Tardivel, A., Castillo, R., Bourquin, C., Guarda, G., Tian, Z., Tschopp, J., & Zhou, R. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.015 · Cited by 784 · see citing works
The role of protein clearance mechanisms in organismal ageing and age-related diseases
Vı́lchez, D., Sáez, I., & Dillin, A. G. (2014) · Nature Communications · doi:10.1038/ncomms6659 · Cited by 684 · see citing works
Canonical 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
Self-citationCutting edge: impaired toll-like receptor expression and function in aging
Renshaw, M., Rockwell, J., Engleman, C., Gewirtz, A., Katz, J., & Sambhara, S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.9.4697 · Cited by 626 · see citing works
Age-related inflammatory cytokines and disease
Brüünsgaard, H., & Pedersen, B. K. (2003) · Immunology and Allergy Clinics of North America · doi:10.1016/s0889-8561(02)00056-5 · Cited by 608 · see citing works
Evans, D. A., Funkenstein, H. H., Albert, M., Scherr, P. A., Cook, N. R., Chown, M. J., Hebert, L. E., Hennekens, C. H., & Taylor, J. O. (1989) · PubMed · Cited by 599 · see citing works
Adipose Tissue Macrophages Promote Myelopoiesis and Monocytosis in Obesity
Nagareddy, P. R., Kraakman, M. J., Masters, S. L., Stirzaker, R. A., Gorman, D. J., Grant, R. W., Dragoljevic, D., Hong, E. S., Abdel‐Latif, A., Smyth, S. S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.029 · Cited by 510 · see citing works
Self-citationMitochondrial oxidative stress in aging and healthspan
Dai, D., Chiao, Y. A., Marcinek, D. J., Szeto, H. H., & Rabinovitch, P. S. (2014) · Longevity & Healthspan · doi:10.1186/2046-2395-3-6 · Cited by 481 · see citing works
Adipose tissue as an immunological organ
Grant, R. W., & Dixit, V. D. (2015) · Obesity · doi:10.1002/oby.21003 · Cited by 453 · see citing works
Self-citationBlaum, C. S., Xue, Q., Michelon, E., Semba, R. D., & Fried, L. P. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53300.x · Cited by 433 · see citing works
Inflammation, ageing and chronic disease
Pawelec, G., Goldeck, D., & Derhovanessian, E. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.03.007 · Cited by 420 · see citing works
Mechanisms of NOD-like Receptor-Associated Inflammasome Activation
Wen, H., Miao, E. A., & Ting, J. P. ‐. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.037 · Cited by 415 · see citing works
Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia
Grathwohl, S. A., Kälin, R. E., Bolmont, T., Prokop, S., Winkelmann, G., Kaeser, S. A., Odenthal, J., Radde, R., Eldh, T., Gandy, S., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2432 · Cited by 401 · 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
Leng, S., Chaves, P., Koenig, K., & Walston, J. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.50315.x · Cited by 387 · see citing works
Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process
Dinarello, C. A. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.2.447s · Cited by 385 · see citing works
Differential Expression of NLRP3 among Hematopoietic Cells
Guarda, G., Zenger, M., Yazdi, A. S., Schroder, K., Ferrero, I., Menu, P., Tardivel, A., Mattmann, C., & Tschopp, J. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002720 · Cited by 350 · see citing works
Pedersen, M., Bruunsgaard, H., Weis, N., Hendel, H. W., Andreassen, B. U., Eldrup, E., Dela, F., & Pedersen, B. K. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00027-7 · Cited by 342 · see citing works
Lumeng, C. N., Liu, J., Geletka, L., Delaney, C., Delproposto, J., Desai, A., Oatmen, K., Martinez-Santibanez, G., Julius, A., Garg, S., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102188 · Cited by 328 · see citing works
β-Amyloid Activates the O⨪2 Forming NADPH Oxidase in Microglia, Monocytes, and Neutrophils
Della Bianca, V., Dusi, S., Bianchini, E., Dal Prà, I., & Rossi, F. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.22.15493 · Cited by 324 · see citing works
Shao, W., Yeretssian, G., Doiron, K., Hussain, S. N. A., & Saleh, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m708182200 · Cited by 321 · see citing works
Asgari, E., Friec, G. L., Yamamoto, H., Perucha, E., Sacks, S. H., Köhl, J., Cook, H. T., & Kemper, C. (2013) · Blood · doi:10.1182/blood-2013-05-502229 · Cited by 311 · see citing works
Obesity accelerates thymic aging
Yang, H., Youm, Y., Vandanmagsar, B., Rood, J. C., Kumar, K. G., Butler, A. A., & Dixit, V. D. (2009) · Blood · doi:10.1182/blood-2009-03-213595 · Cited by 309 · see citing works
Self-citationCholesterol Crystals Induce Complement-Dependent Inflammasome Activation and Cytokine Release
Samstad, E. O., Niyonzima, N., Nymo, S. H., Aune, M. H., Ryan, L., Bakke, S. S., Lappegård, K. T., Brekke, O., Lambris, J. D., Damås, J. K., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302484 · Cited by 286 · see citing works
Boehmer, E. D., Góral, J., Faunce, D. E., & Kovacs, E. J. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0803389 · Cited by 266 · see citing works
Prevalence of obesity among older adults in the United States, 2007-2010.
Fakhouri, T. H. I., Ogden, C. L., Carroll, M. D., Kit, B. K., & Flegal, K. M. (2012) · PubMed · Cited by 265 · see citing works
Snodgrass, R. G., Huang, S., Choi, I.-W., Rutledge, J. C., & Hwang, D. H. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300298 · Cited by 243 · see citing works
Williams-Bey, Y., Boularan, C., Vural, A., Huang, N.-N., Hwang, I.-Y., Shan-Shi, C., & Kehrl, J. H. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097957 · Cited by 215 · see citing works
D-beta-hydroxybutyrate extends lifespan in C. elegans
Edwards, C., Canfield, J., Copes, N., Rehan, M., Lipps, D., & Bradshaw, P. C. (2014) · Aging · doi:10.18632/aging.100683 · Cited by 203 · see citing works
Rochon, J., Bales, C. W., Ravussin, É., Redman, L. M., Holloszy, J. O., Racette, S. B., Roberts, S. B., Das, S. K., Romashkan, S., Galan, K. M., et al. (2010) · The Journals of Gerontology Series A · doi:10.1093/gerona/glq168 · Cited by 203 · see citing works
Cutting Edge: The NLRP3 Inflammasome Links Complement-Mediated Inflammation and IL-1β Release
Laudisi, F., Spreafico, R., Evrard, M., Hughes, T. R., Mandriani, B., Kandasamy, M., Morgan, B. P., Sivasankar, B., & Mortellaro, A. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300489 · Cited by 198 · see citing works
Yang, H., Youm, Y.-H., & Dixit, V. D. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900562 · Cited by 196 · see citing works
Self-citationNLRP3 Inflammasomes Show High Expression in Aorta of Patients with Atherosclerosis
Zheng, F. Y., Xing, S., Gong, Z., & Xing, Q. (2013) · Heart Lung and Circulation · doi:10.1016/j.hlc.2013.01.012 · Cited by 191 · see citing works
Hickey, T. (1980) · Brooks/Cole Pub. Co. eBooks · Cited by 176 · see citing works
Infectious Agents Are Not Necessary for Murine Atherogenesis
Wright, S. D., Burton, C., Hernandez, M., Hassing, H., Montenegro, J., Mundt, S., Patel, S., Card, D. J., Hermanowski-Vosatka, A., Bergstrom, J. D., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.8.1437 · Cited by 176 · see citing works
Elimination of the NLRP3-ASC Inflammasome Protects against Chronic Obesity-Induced Pancreatic Damage
Youm, Y., Adijiang, A., Vandanmagsar, B., Burk, D. H., Ravussin, A., & Dixit, V. D. (2011) · Endocrinology · doi:10.1210/en.2011-1326 · Cited by 175 · see citing works
Self-citationThe Nlrp3 inflammasome promotes age-related thymic demise and immunosenescence
Youm, Y.-H., Kanneganti, T.-D., Vandanmagsar, B., Zhu, X., Ravussin, A., Adijiang, A., Owen, J. S., Thomas, M. J., Francis, J., Parks, J. S., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2011.11.005 · Cited by 172 · see citing works
Self-citationGoto, M. (2008) · PubMed · Cited by 154 · see citing works
Subfield History: Caloric Restriction, Slowing Aging, and Extending Life
Masoro, E. J. (2003) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2003.8.re2 · Cited by 149 · see citing works
Bonar, S. L., Brydges, S., Mueller, J., McGeough, M. D., Peña, C., Chen, D., Grimston, S., Hickman-Brecks, C. L., Ravindran, S., McAlinden, A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035979 · Cited by 130 · see citing works
Arthropathy of neonatal onset multisystem inflammatory disease (NOMID/CINCA)
Hill, S. C., Namde, M., Dwyer, A. A., Poznanski, A. K., Canna, S., & Goldbach‐Mansky, R. T. (2006) · Pediatric Radiology · doi:10.1007/s00247-006-0358-0 · Cited by 125 · see citing works
Cross-regulation between the IL-1β/IL-18 processing inflammasome and other inflammatory cytokines
Barker, B. R., Taxman, D. J., & Ting, J. P. ‐. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.07.005 · Cited by 124 · see citing works
Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers
Mariño, G., Pietrocola, F., Madeo, F., & Kroemer, G. (2014) · Autophagy · doi:10.4161/auto.36413 · Cited by 107 · see citing works
Masino, S. A., & Ruskin, D. N. (2013) · Journal of Child Neurology · doi:10.1177/0883073813487595 · Cited by 94 · see citing works
The Frailty Syndrome: Clinical measurements and basic underpinnings in humans and animals
Mohler, M. J., Fain, M. J., Wertheimer, A. M., Najafi, B., & Nikolich‐Žugich, J. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.024 · Cited by 85 · see citing works
Fontana, L., Addante, F., Copetti, M., Paroni, G., Fontana, A., Sancarlo, D., Pellegrini, F., Ferrucci, L., & Pilotto, A. (2013) · Aging Cell · doi:10.1111/acel.12068 · Cited by 72 · see citing works
Complement C5a potentiates uric acid crystal‐induced IL‐1β production
An, L., Mehta, P., Xu, L., Turman, S., Reimer, T., Naiman, B. M., Connor, J. R., Sanjuán, M. A. F., Kolbeck, R., & Fung, M. S. C. (2014) · European Journal of Immunology · doi:10.1002/eji.201444560 · Cited by 71 · see citing works
Wang, L., Qu, P., Zhao, J., & Chang, Y. (2014) · Archives of Medical Science · doi:10.5114/aoms.2014.44871 · Cited by 71 · see citing works
Impact of immune-metabolic interactions on age-related thymic demise and T cell senescence
Dixit, V. D. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.002 · Cited by 68 · see citing works
Self-citationKrone, C. L., Trzciński, K., Zborowski, T., Sanders, E. A. M., & Bogaert, D. (2013) · Infection and Immunity · doi:10.1128/iai.00618-13 · Cited by 63 · see citing works
Chronic caloric restriction partially protects against age-related alteration in serum metabolome
Guzman, J. M. D., Ku, G., Fahey, R., Youm, Y., Kass, I. J., Ingram, D. K., Dixit, V. D., & Kheterpal, I. (2012) · AGE · doi:10.1007/s11357-012-9430-x · Cited by 57 · see citing works
Self-citationD-beta-Hydroxybutyrate Extends Lifespan in
Edwards, C., Canfield, J., Copes, N., Rehan, M., Lipps, D., & Bradshaw, P. C. (2014) · Digital Commons - University of South Florida (University of South Florida) · Cited by 34 · see citing works
Inflammasome Activation by Altered Proteostasis
Shin, J. N., Fattah, E. A., Bhattacharya, A., Ko, S., & Eissa, N. T. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.514919 · Cited by 32 · see citing works
Miller, R. A., Kreider, J. M., Gałecki, A. T., et al. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00671.x · Cited by 19 · see citing works
Recent Advances: Osteoporosis in the “Oldest Old”
Colon-Emeric, C. S. (2013) · Current Osteoporosis Reports · doi:10.1007/s11914-013-0158-z · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
Ferrucci, L., & Fabbri, E. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0064-2 · Cited by 3,690 · see citing works
Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines
Rea, I. M., Gibson, D. S., McGilligan, V., McNerlan, S. E., Alexander, H. D., & Ross, O. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00586 · Cited by 1,267 · see citing works
Franceschi, C., Garagnani, P., Vitale, G., Capri, M., & Salvioli, S. (2017) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.09.005 · Cited by 997 · see citing works
β-Hydroxybutyrate: A Signaling Metabolite
Newman, J. C., & Verdin, E. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064916 · Cited by 872 · see citing works
NLRP3 inflammasome and its inhibitors: a review
Shao, B.-Z., Xu, Z.-Q., Han, B.-Z., Su, D.-F., & Liu, C. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00262 · Cited by 836 · see citing works
“…protect against disease and death, inappropriate activation of the NLRP3 inflammasome can contribute to the onset and progression of various diseases, particularly age-related diseases such as metabolic disorders and metabolic syndrome (Franceschi et al., 2000; Goldberg and Dixit, 2015).”
BackgroundRethinking IL-6 and CRP: Why they are more than inflammatory biomarkers, and why it matters
Del Giudice, M., & Gangestad, S. W. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.02.013 · Cited by 779 · see citing works
Metabolic Control of Longevity
López-Otín, C., Galluzzi, L., Freije, J. M. P., Madeo, F., & Kroemer, G. (2016) · Cell · doi:10.1016/j.cell.2016.07.031 · Cited by 753 · see citing works
Immune response, inflammation, and the clinical spectrum of COVID-19
García, L. F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01441 · Cited by 739 · 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
Bennett, J. M., Reeves, G., Billman, G. E., & Sturmberg, J. P. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00316 · Cited by 531 · see citing works
Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice
Newman, J. C., Covarrubias, A. J., Zhao, M., Yu, X., Gut, P., Ng, C.-P., Huang, Y., Haldar, S., & Verdin, E. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.004 · Cited by 493 · see citing works
Han, X., Sun, S., Sun, Y., Song, Q., Zhu, J., Song, N., Chen, M., Sun, T., Xia, M., Ding, J., et al. (2019) · Autophagy · doi:10.1080/15548627.2019.1596481 · Cited by 408 · see citing works
SenNet recommendations for detecting senescent cells in different tissues
Suryadevara, V., Hudgins, A. D., Rajesh, A., Pappalardo, A., Karpova, A., Dey, A. K., Hertzel, A., Agudelo, A., Rocha, A., Soygur, B., et al. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00738-8 · Cited by 408 · see citing works
“75–78).”
β-hydroxybutyrate deactivates neutrophil NLRP3 inflammasome to relieve gout flares
Goldberg, E. L., Asher, J. L., Molony, R. D., Shaw, A. C., Zeiss, C. J., Wang, C., Morozova-Roche, L. A., Herzog, R. I., Iwasaki, A., & Dixit, V. D. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.004 · Cited by 370 · see citing works
Self-citationThe 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
Tissue Stem Cells: Architects of Their Niches
Fuchs, E., & Blau, H. M. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.09.011 · Cited by 332 · see citing works
Evaluation of inflammation and follicle depletion during ovarian ageing in mice
Lliberos, C., Liew, S. H., Zareie, P., La Gruta, N. L., Mansell, A., & Hutt, K. (2021) · Scientific Reports · doi:10.1038/s41598-020-79488-4 · Cited by 247 · see citing works
Peripheral 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
Necroptosis contributes to chronic inflammation and fibrosis in aging liver
Mohammed, S., Thadathil, N., Selvarani, R., Nicklas, E. H., Wang, D., Miller, B. F., Richardson, A., & Deepa, S. S. (2021) · Aging Cell · doi:10.1111/acel.13512 · Cited by 192 · see citing works
Ritzel, R. M., Doran, S. J., Glaser, E. P., Meadows, V. E., Faden, A. I., Stoica, B. A., & Loane, D. J. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.02.010 · Cited by 156 · see citing works
Mohorko, N., Černelič-Bizjak, M., Poklar-Vatovec, T., Grom, G., Kenig, S., Petelin, A., & Jenko-Pražnikar, Z. (2019) · Nutrition Research · doi:10.1016/j.nutres.2018.11.007 · Cited by 147 · see citing works
Metformin and ageing: improving ageing outcomes beyond glycaemic control
Valencia, W. M., Palacio, A., Tamariz, L., & Florez, H. (2017) · Diabetologia · doi:10.1007/s00125-017-4349-5 · Cited by 142 · see citing works
The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
Picca, A., Lezza, A. M. S., Leeuwenburgh, C., Pesce, V., Calvani, R., Bossola, M., Manes-Gravina, E., Landi, F., Bernabei, R., & Marzetti, E. (2018) · Rejuvenation Research · doi:10.1089/rej.2017.1989 · Cited by 144 · see citing works
Cellular senescence, senescence-associated secretory phenotype, and chronic kidney disease
Wang, W.-J., Cai, G.-Y., & Chen, X.-M. (2017) · Oncotarget · doi:10.18632/oncotarget.17327 · Cited by 121 · see citing works
Impact of resistance training on the autophagy-inflammation-apoptosis crosstalk in elderly subjects
Mejías-Peña, Y., Estébanez, B., Rodriguez-Miguelez, P., Fernandez-Gonzalo, R., Almar, M., de Paz, J. A., González-Gallego, J., & Cuevas, M. J. (2017) · Aging · doi:10.18632/aging.101167 · Cited by 102 · see citing works
“Emerging evidence suggests that pro-inflammatory cytokines IL-1 and IL-18 show an age-dependent regulation, which seems to implicate inflammasomemediated caspase-1 activation in the aging process [18].”
BackgroundSliz, E., Kalaoja, M., Ahola-Olli, A., Raitakari, O., Perola, M., Salomaa, V., Lehtimäki, T., Karhu, T., Viinamäki, H., Salmi, M., et al. (2019) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2018-105965 · Cited by 60 · see citing works
Cullen, N. C., Mälarstig, A. N., Stomrud, E., Hansson, O., & Mattsson-Carlgren, N. (2021) · Scientific Reports · doi:10.1038/s41598-021-81705-7 · Cited by 62 · see citing works
Effects of Dietary Restriction on Adipose Mass and Biomarkers of Healthy Aging in Human
Lettieri-Barbato, D., Giovannetti, E., & Aquilano, K. (2016) · Aging · doi:10.18632/aging.101122 · Cited by 57 · see citing works
Metformin monotherapy downregulates diabetes-associated inflammatory status and impacts on mortality
Tizazu, A. M., Nyunt, M. S. Z., Cexus, O., Suku, K., Mok, E., Xian, C. H., Chong, J., Tan, C., How, W., Hubert, S., et al. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00572 · Cited by 37 · see citing works
NLRP3 inflammasome: common nexus between depression and cardiovascular diseases
Alcocer-Gómez, E., & Cordero, M. D. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.214 · Cited by 20 · see citing works
Exploring the anti-aging effects of fisetin in telomerase-deficient progeria mouse model
Zhao, R., Kou, H., Jiang, D., & Wang, F. (2023) · PeerJ · doi:10.7717/peerj.16463 · Cited by 18 · see citing works
“The implications of aging, as a major risk factor for various chronic diseases ( Goldberg & Dixit, 2015 ), highlight the urgent need for innovative medical interventions and healthcare models.”
Background
- Authors
- Goldberg, E. L., & Dixit, V. D.
- Affiliations
- Yale University (US)
- Corresponding author
- Dixit, Vishwa Deep
- Venue
- Immunological Reviews
- Publisher
- Wiley
- Published
- 2015-04-16
- Volume
- 265
- Issue
- 1
- Pages
- 63-74
- ISSN
- 0105-2896 (ISSN-L)
- 1600-065X
- PMC
- PMC4400872
- OpenAlex
- W1995481571
- Cited by
- 274
- References
- 91
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 27 · 2023: 29 · 2022: 27 · 2021: 34 · 2020: 31 · 2019: 32 · 2018: 24 · 2017: 22 · 2016: 10 · 2015: 7
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Immunological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (AI105097, AG043608, DK090556, AG045712)
- 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
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- age-related inflammation, healthspan extension, NLRP3 inflammasome, caspase-1 activation, interleukin-1, IL-18, damage-associated molecular patterns, myeloid cells, insulin resistance, bone loss, cognitive decline, frailty
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Aging, Animals, Carrier Proteins, Humans, Inflammation, Interleukin-1, Caspase 1, Myeloid Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
