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  • Perspective
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Chronic inflammation in the etiology of disease across the life span

Nature Medicine volume 25, pages 1822–1832 (2019)Cite this article

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Abstract

Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.

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Fig. 1: Causes and consequences of low-grade systemic chronic inflammation.
Fig. 2: The maternal exposome and low-grade systemic chronic inflammation.
Fig. 3: Inflammatory model of immunosenescence and chronic disease.

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References

  1. Furman, D. et al. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat. Med. 23, 174–184 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Netea, M. G. et al. A guiding map for inflammation. Nat. Immunol. 18, 826–831 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Slavich, G. M. Understanding inflammation, its regulation, and relevance for health: a top scientific and public priority. Brain Behav. Immun. 45, 13–14 (2015).

    Article  PubMed  Google Scholar 

  4. Bennett, J. M., Reeves, G., Billman, G. E. & Sturmberg, J. P. Inflammation–nature’s way to efficiently respond to all types of challenges: implications for understanding and managing “the epidemic” of chronic diseases. Front. Med. 5, 316 (2018).

    Article  Google Scholar 

  5. GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1736–1788 (2018).

    Article  Google Scholar 

  6. Miller, G. E., Chen, E. & Parker, K. J. Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving toward a model of behavioral and biological mechanisms. Psychol. Bull. 137, 959–997 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Fleming, T. P. et al. Origins of lifetime health around the time of conception: causes and consequences. Lancet 391, 1842–1852 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Renz, H. et al. An exposome perspective: early-life events and immune development in a changing world. J. Allergy Clin. Immunol. 140, 24–40 (2017).

    Article  PubMed  Google Scholar 

  9. Kotas, M. E. & Medzhitov, R. Homeostasis, inflammation, and disease susceptibility. Cell 160, 816–827 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Straub, R. H., Cutolo, M., Buttgereit, F. & Pongratz, G. Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J. Intern. Med. 267, 543–560 (2010).

    Article  CAS  PubMed  Google Scholar 

  11. Straub, R. H., Cutolo, M. & Pacifici, R. Evolutionary medicine and bone loss in chronic inflammatory diseases—a theory of inflammation-related osteopenia. Semin. Arthritis Rheum. 45, 220–228 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Straub, R. H. & Schradin, C. Chronic inflammatory systemic diseases: an evolutionary trade-off between acutely beneficial but chronically harmful programs. Evol. Med. Public Health 2016, 37–51 (2016).

    PubMed  PubMed Central  Google Scholar 

  13. Straub, R. H. The brain and immune system prompt energy shortage in chronic inflammation and ageing. Nat. Rev. Rheumatol. 13, 743–751 (2017).

    Article  CAS  PubMed  Google Scholar 

  14. Slavich, G. M. Psychoneuroimmunology of stress and mental health. in The Oxford Handbook of Stress and Mental Health (eds K. Harkness & E. P. Hayden) (Oxford University Press, in the press).

  15. Fullerton, J. N. & Gilroy, D. W. Resolution of inflammation: a new therapeutic frontier. Nat. Rev. Drug Discov. 15, 551–567 (2016).

    Article  CAS  PubMed  Google Scholar 

  16. Calder, P. C. et al. A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies. Br. J. Nutr. 109, S1–S34 (2013).

    Article  PubMed  Google Scholar 

  17. Taniguchi, K. & Karin, M. NF-κB, inflammation, immunity and cancer: coming of age. Nat. Rev. Immunol. 18, 309–324 (2018).

    Article  CAS  PubMed  Google Scholar 

  18. Gisterå, A. & Hansson, G. K. The immunology of atherosclerosis. Nat Rev. Nephrol. 13, 368–380 (2017).

    Article  PubMed  CAS  Google Scholar 

  19. Ferrucci, L. & Fabbri, E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat. Rev. Cardiol. 15, 505–522 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Heneka, M. T., Kummer, M. P. & Latz, E. Innate immune activation in neurodegenerative disease. Nat. Rev. Immunol. 14, 463–477 (2014).

    Article  CAS  PubMed  Google Scholar 

  21. Miller, A. H. & Raison, C. L. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat. Rev. Immunol. 16, 22–34 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shen-Orr, S. S. et al. Defective signaling in the JAK-STAT pathway tracks with chronic inflammation and cardiovascular risk in aging humans. Cell Syst. 3, 374–384.e4 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Verschoor, C. P. et al. Serum C-reactive protein and congestive heart failure as significant predictors of herpes zoster vaccine response in elderly nursing home residents. J. Infect. Dis. 216, 191–197 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Fourati, S. et al. Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination. Nat. Commun. 7, 10369 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. McDade, T. W., Adair, L., Feranil, A. B. & Kuzawa, C. Positive antibody response to vaccination in adolescence predicts lower C-reactive protein concentration in young adulthood in the Philippines. Am. J. Hum. Biol. 23, 313–318 (2011).

    Article  PubMed  Google Scholar 

  26. Singer, K. & Lumeng, C. N. The initiation of metabolic inflammation in childhood obesity. J. Clin. Invest. 127, 65–73 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Olvera Alvarez, H. A., Kubzansky, L. D., Campen, M. J. & Slavich, G. M. Early life stress, air pollution, inflammation, and disease: an integrative review and immunologic model of social-environmental adversity and lifespan health. Neurosci. Biobehav. Rev. 92, 226–242 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Serhan, C. N. Pro-resolving lipid mediators are leads for resolution physiology. Nature 510, 92–101 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Serhan, C. N. & Levy, B. D. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. J. Clin. Invest. 128, 2657–2669 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Franceschi, C., Garagnani, P., Vitale, G., Capri, M. & Salvioli, S. Inflammaging and ‘garb-aging’. Trends Endocrinol. Metab. 28, 199–212 (2017).

    Article  CAS  PubMed  Google Scholar 

  31. Liston, A. & Masters, S. L. Homeostasis-altering molecular processes as mechanisms of inflammasome activation. Nat. Rev. Immunol. 17, 208–214 (2017).

    Article  CAS  PubMed  Google Scholar 

  32. Frank, D. & Vince, J. E. Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ. 26, 99–114 (2019).

    Article  PubMed  Google Scholar 

  33. Jin, C., Henao-Mejia, J. & Flavell, R. A. Innate immune receptors: key regulators of metabolic disease progression. Cell Metab. 17, 873–882 (2013).

    Article  CAS  PubMed  Google Scholar 

  34. Hotamisligil, G. S. Inflammation, metaflammation and immunometabolic disorders. Nature 542, 177–185 (2017).

    Article  CAS  PubMed  Google Scholar 

  35. Kazankov, K. et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat. Rev. Gastroenterol. Hepatol. 16, 145–159 (2019).

    Article  CAS  PubMed  Google Scholar 

  36. Redlich, K. & Smolen, J. S. Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat. Rev. Drug Discov. 11, 234–250 (2012).

    Article  CAS  PubMed  Google Scholar 

  37. Zhang, J. et al. The risk of metabolic syndrome in patients with rheumatoid arthritis: a meta-analysis of observational studies. PLoS One 8, e78151 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Armstrong, A. W., Harskamp, C. T. & Armstrong, E. J. Psoriasis and the risk of diabetes mellitus: a systematic review and meta-analysis. JAMA Dermatol. 149, 84–91 (2013).

    Article  PubMed  Google Scholar 

  39. Dregan, A., Charlton, J., Chowienczyk, P. & Gulliford, M. C. Chronic inflammatory disorders and risk of type 2 diabetes mellitus, coronary heart disease, and stroke: a population-based cohort study. Circulation 130, 837–844 (2014).

    Article  CAS  PubMed  Google Scholar 

  40. Ridker, P. M. A test in context: high-sensitivity C-reactive protein. J. Am. Coll. Cardiol. 67, 712–723 (2016).

    Article  PubMed  Google Scholar 

  41. Emerging Risk Factors Collaboration. et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 375, 132–140 (2010).

    Article  CAS  Google Scholar 

  42. Burska, A. N., Sakthiswary, R. & Sattar, N. Effects of tumour necrosis factor antagonists on insulin sensitivity/resistance in rheumatoid arthritis: a systematic review and meta-analysis. PLoS One 10, e0128889 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Chou, R. et al. Treatment for rheumatoid arthritis and risk of Alzheimer’s disease: a nested case-control analysis. CNS Drugs 30, 1111–1120 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).

    Article  CAS  PubMed  Google Scholar 

  45. Proctor, M. J. et al. Systemic inflammation predicts all-cause mortality: a Glasgow inflammation outcome study. PLoS One 10, e0116206 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Arai, Y. et al. Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians. EBioMedicine 2, 1549–1558 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Roubenoff, R. et al. Monocyte cytokine production in an elderly population: effect of age and inflammation. J. Gerontol. A Biol. Sci. Med. Sci. 53, M20–M26 (1998).

    Article  CAS  PubMed  Google Scholar 

  48. Ahluwalia, N. et al. Cytokine production by stimulated mononuclear cells did not change with aging in apparently healthy, well-nourished women. Mech. Ageing Dev. 122, 1269–1279 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Beharka, A. A. et al. Interleukin-6 production does not increase with age. J. Gerontol. A Biol. Sci. Med. Sci. 56, B81–B8 (2001).

    Article  CAS  PubMed  Google Scholar 

  50. Elisia, I. et al. Effect of age on chronic inflammation and responsiveness to bacterial and viral challenges. PLoS One 12, e0188881 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Morrisette-Thomas, V. et al. Inflamm-aging does not simply reflect increases in pro-inflammatory markers. Mech. Ageing Dev. 139, 49–57 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Alpert, A. et al. A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring. Nat. Med. 25, 487–495 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Coppé, J.-P., Desprez, P.-Y., Krtolica, A. & Campisi, J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Zhu, Y., Armstrong, J. L., Tchkonia, T. & Kirkland, J. L. Cellular senescence and the senescent secretory phenotype in age-related chronic diseases. Curr. Opin. Clin. Nutr. Metab. Care 17, 324–328 (2014).

    Article  CAS  PubMed  Google Scholar 

  55. Kennedy, B. K. et al. Geroscience: linking aging to chronic disease. Cell 159, 709–713 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Campisi, J. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 75, 685–705 (2013).

    Article  CAS  PubMed  Google Scholar 

  57. Effros, R. B. The silent war of CMV in aging and HIV infection. Mech. Ageing Dev. 158, 46–52 (2016).

    Article  PubMed  Google Scholar 

  58. Stout, M. B., Justice, J. N., Nicklas, B. J. & Kirkland, J. L. Physiological aging: links among adipose tissue dysfunction, diabetes, and frailty. Physiology (Bethesda) 32, 9–19 (2017).

    CAS  Google Scholar 

  59. Franceschi, C., Garagnani, P., Parini, P., Giuliani, C. & Santoro, A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat. Rev. Endocrinol. 159, 1–15 (2018).

    Google Scholar 

  60. Zitvogel, L., Pietrocola, F. & Kroemer, G. Nutrition, inflammation and cancer. Nat. Immunol. 18, 843–850 (2017).

    Article  CAS  PubMed  Google Scholar 

  61. Razzoli, M. et al. Social stress shortens lifespan in mice. Aging Cell 17, e12778 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Carroll, J. E. et al. Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans. Brain Behav. Immun. 51, 223–229 (2016).

    Article  CAS  PubMed  Google Scholar 

  63. Yuan, J. et al. Long-term persistent organic pollutants exposure induced telomere dysfunction and senescence-associated secretary phenotype. J. Gerontol. A Biol. Sci. Med. Sci. 73, 1027–1035 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Shen-Orr, S. S. & Furman, D. Variability in the immune system: of vaccine responses and immune states. Curr. Opin. Immunol. 25, 542–547 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. McDade, T. W. Early environments and the ecology of inflammation. Proc. Natl Acad. Sci. USA 109, 17281–17288 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Carrera-Bastos, P., Fontes-Villalba, M., O’Keefe, J. H., Lindeberg, S. & Cordain, L. The western diet and lifestyle and diseases of civilization. Res. Rep. Clin. Cardiol. 2, 15–35 (2011).

    Google Scholar 

  67. Raichlen, D. A. et al. Physical activity patterns and biomarkers of cardiovascular disease risk in hunter-gatherers. Am. J. Hum. Biol. 29, e22919 (2017).

    Article  Google Scholar 

  68. Kaplan, H. et al. Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study. Lancet 389, 1730–1739 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Lindeberg, S. & Lundh, B. Apparent absence of stroke and ischaemic heart disease in a traditional Melanesian island: a clinical study in Kitava. J. Intern. Med. 233, 269–275 (1993).

    Article  CAS  PubMed  Google Scholar 

  70. Lindeberg, S., Berntorp, E., Nilsson-Ehle, P., Terént, A. & Vessby, B. Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava Study. Am. J. Clin. Nutr. 66, 845–852 (1997).

    Article  CAS  PubMed  Google Scholar 

  71. Lindeberg, S., Eliasson, M., Lindahl, B. & Ahrén, B. Low serum insulin in traditional Pacific Islanders—the Kitava Study. Metabolism 48, 1216–1219 (1999).

    Article  CAS  PubMed  Google Scholar 

  72. Brodin, P. et al. Variation in the human immune system is largely driven by non-heritable influences. Cell 160, 37–47 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Niedzwiecki, M. M. et al. The exposome: molecules to populations. Annu. Rev. Pharmacol. Toxicol. 59, 107–127 (2019).

    Article  CAS  PubMed  Google Scholar 

  74. Virgin, H. W., Wherry, E. J. & Ahmed, R. Redefining chronic viral infection. Cell 138, 30–50 (2009).

    Article  CAS  PubMed  Google Scholar 

  75. Wang, C. et al. Effects of aging, cytomegalovirus infection, and EBV infection on human B cell repertoires. J. Immunol. 192, 603–611 (2014).

    Article  CAS  PubMed  Google Scholar 

  76. Petta, S. et al. Hepatitis C virus infection is associated with increased cardiovascular mortality: a meta-analysis of observational studies. Gastroenterology 150, 145–155.e4 (2016).

    Article  PubMed  Google Scholar 

  77. Root-Bernstein, R. & Fairweather, D. Complexities in the relationship between infection and autoimmunity. Curr. Allergy Asthma Rep. 14, 407 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Furman, D. et al. Cytomegalovirus infection enhances the immune response to influenza. Sci. Transl. Med. 7, 281ra43 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Pawelec, G. et al. Human immunosenescence: is it infectious? Immunol. Rev. 205, 257–268 (2005).

    Article  CAS  PubMed  Google Scholar 

  80. Chou, J. P., Ramirez, C. M., Wu, J. E. & Effros, R. B. Accelerated aging in HIV/AIDS: novel biomarkers of senescent human CD8+ T cells. PLoS One 8, e64702 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Sochocka, M., Zwolińska, K. & Leszek, J. The infectious etiology of Alzheimer’s disease. Curr. Neuropharmacol. 15, 996–1009 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Rook, G., Bäckhed, F., Levin, B. R., McFall-Ngai, M. J. & McLean, A. R. Evolution, human-microbe interactions, and life history plasticity. Lancet 390, 521–530 (2017).

    Article  PubMed  Google Scholar 

  83. McDade, T. W. et al. Analysis of variability of high sensitivity C-reactive protein in lowland Ecuador reveals no evidence of chronic low-grade inflammation. Am. J. Hum. Biol. 24, 675–681 (2012).

    Article  PubMed  Google Scholar 

  84. Liebert, M. A. et al. Implications of market integration for cardiovascular and metabolic health among an indigenous Amazonian Ecuadorian population. Ann. Hum. Biol. 40, 228–242 (2013).

    Article  PubMed  Google Scholar 

  85. Eriksson, U. K., van Bodegom, D., May, L., Boef, A. G. C. & Westendorp, R. G. J. Low C-reactive protein levels in a traditional West-African population living in a malaria endemic area. PLoS One 8, e70076 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Agmon-Levin, N. et al. Antitreponemal antibodies leading to autoantibody production and protection from atherosclerosis in Kitavans from Papua New Guinea. Ann. N. Y. Acad. Sci. 1173, 675–682 (2009).

    Article  CAS  PubMed  Google Scholar 

  87. Gurven, M., Jaeggi, A. V., Kaplan, H. & Cummings, D. Physical activity and modernization among Bolivian Amerindians. PLoS One 8, e55679 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Cordain, L. et al. Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets. Am. J. Clin. Nutr. 71, 682–692 (2000).

    Article  CAS  PubMed  Google Scholar 

  89. Kuipers, R. S., Joordens, J. C. A. & Muskiet, F. A. J. A multidisciplinary reconstruction of Palaeolithic nutrition that holds promise for the prevention and treatment of diseases of civilisation. Nutr. Res. Rev. 25, 96–129 (2012).

    Article  PubMed  Google Scholar 

  90. De la Iglesia, H. O. et al. Ancestral sleep. Curr. Biol. 26, R271–R272 (2016).

    Article  PubMed  CAS  Google Scholar 

  91. Slavich, G. M. & Cole, S. W. The emerging field of human social genomics. Clin. Psychol. Sci. 1, 331–348 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Chakravarthy, M. V. & Booth, F. W. Eating, exercise, and ‘thrifty’ genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. J. Appl. Physiol. 96, 3–10 (2004).

    Article  PubMed  Google Scholar 

  93. Hallal, P. C. et al. Global physical activity levels: surveillance progress, pitfalls, and prospects. Lancet 380, 247–257 (2012).

    Article  PubMed  Google Scholar 

  94. Katzmarzyk, P. T., Lee, I.-M., Martin, C. K. & Blair, S. N. Epidemiology of physical activity and exercise training in the United States. Prog. Cardiovasc. Dis. 60, 3–10 (2017).

    Article  PubMed  Google Scholar 

  95. Fiuza-Luces, C. et al. Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors. Nat. Rev. Cardiol. 15, 731–743 (2018).

    Article  CAS  PubMed  Google Scholar 

  96. Breen, L. et al. Two weeks of reduced activity decreases leg lean mass and induces ‘anabolic resistance’ of myofibrillar protein synthesis in healthy elderly. J. Clin. Endocrinol. Metab. 98, 2604–2612 (2013).

    Article  CAS  PubMed  Google Scholar 

  97. Fedewa, M. V., Hathaway, E. D. & Ward-Ritacco, C. L. Effect of exercise training on C reactive protein: a systematic review and meta-analysis of randomised and non-randomised controlled trials. Br. J. Sports Med. 51, 670–676 (2017).

    Article  PubMed  Google Scholar 

  98. Meneses-Echávez, J. F. et al. The effect of exercise training on mediators of inflammation in breast cancer survivors: a systematic review with meta-analysis. Cancer Epidemiol. Biomarkers Prev. 25, 1009–1017 (2016).

    Article  PubMed  CAS  Google Scholar 

  99. Hayashino, Y. et al. Effects of exercise on C-reactive protein, inflammatory cytokine and adipokine in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Metab. Clin. Exp. 63, 431–440 (2014).

    Article  CAS  PubMed  Google Scholar 

  100. Booth, F. W., Roberts, C. K. & Laye, M. J. Lack of exercise is a major cause of chronic diseases. Compr. Physiol. 2, 1143–1211 (2012).

    PubMed  PubMed Central  Google Scholar 

  101. Wahid, A. et al. Quantifying the association between physical activity and cardiovascular disease and diabetes: a systematic review and meta-analysis. J. Am. Heart Assoc. 5, e002495 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Moore, S. C. et al. Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults. JAMA Intern. Med. 176, 816–825 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Santos-Lozano, A. et al. Physical activity and Alzheimer disease: a protective association. Mayo. Clin. Proc. 91, 999–1020 (2016).

    Article  PubMed  Google Scholar 

  104. Pérez, L. M. et al. ‘Adipaging’: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue. J. Physiol. 594, 3187–3207 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Schipper, H. S., Prakken, B., Kalkhoven, E. & Boes, M. Adipose tissue-resident immune cells: key players in immunometabolism. Trends Endocrinol. Metabol. 23, 407–415 (2012).

    Article  CAS  Google Scholar 

  106. Tchernof, A. & Després, J.-P. Pathophysiology of human visceral obesity: an update. Physiol. Rev. 93, 359–404 (2013).

    Article  CAS  PubMed  Google Scholar 

  107. Pellegrinelli, V., Carobbio, S. & Vidal-Puig, A. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia 59, 1075–1088 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Frasca, D., Blomberg, B. B. & Paganelli, R. Aging, obesity, and inflammatory age-related diseases. Front. Immunol. 8, 1745 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Grant, R. W. & Dixit, V. D. Adipose tissue as an immunological organ. Obesity (Silver Spring) 23, 512–518 (2015).

    Article  CAS  Google Scholar 

  110. Versini, M., Jeandel, P.-Y., Rosenthal, E. & Shoenfeld, Y. Obesity in autoimmune diseases: not a passive bystander. Autoimm. Rev. 13, 981–1000 (2014).

    Article  CAS  Google Scholar 

  111. Himbert, C. et al. Signals from the adipose microenvironment and the obesity-cancer link–a systematic review. Cancer Prev. Res. (Phila.) 10, 494–506 (2017).

    Article  CAS  Google Scholar 

  112. van Dijk, G. et al. Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration. Front. Neurosci. 9, 173 (2015).

    PubMed  PubMed Central  Google Scholar 

  113. NCD Risk Factor Collaboration (NCD-RisC). et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet 390, 2627–2642 (2017).

    Article  Google Scholar 

  114. Cani, P. D. & Jordan, B. F. Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer. Nat. Rev. Gastroenterol. Hepatol. 15, 671–682 (2018).

    Article  CAS  PubMed  Google Scholar 

  115. Le Chatelier, E. et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541–546 (2013).

    Article  PubMed  CAS  Google Scholar 

  116. Aron-Wisnewsky, J. et al. Major microbiota dysbiosis in severe obesity: fate after bariatric surgery. Gut 68, 70–82 (2019).

    Article  CAS  PubMed  Google Scholar 

  117. Sturgeon, C. & Fasano, A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers 4, e1251384 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Jayashree, B. et al. Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. Mol. Cell. Biochem. 388, 203–210 (2014).

    Article  CAS  PubMed  Google Scholar 

  119. Küme, T. et al. The relationship between serum zonulin level and clinical and laboratory parameters of childhood obesity. J. Clin. Res. Pediatr. Endocrinol. 9, 31–38 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Qi, Y. et al. Intestinal permeability biomarker zonulin is elevated in healthy aging. J. Am. Med. Direc. Assoc. 18, 810.e1–810.e4 (2017).

    Article  Google Scholar 

  121. Le Bastard, Q. et al. Systematic review: human gut dysbiosis induced by non-antibiotic prescription medications. Aliment. Pharmacol. Ther. 47, 332–345 (2018).

    Article  PubMed  Google Scholar 

  122. Bjarnason, I. et al. Mechanisms of damage to the gastrointestinal tract from nonsteroidal anti-inflammatory drugs. Gastroenterology 154, 500–514 (2018).

    Article  CAS  PubMed  Google Scholar 

  123. Sonnenburg, E. D. & Sonnenburg, J. L. The ancestral and industrialized gut microbiota and implications for human health. Nat. Rev. Microbiol. 17, 383–390 (2019).

    Article  CAS  PubMed  Google Scholar 

  124. Bentley, J. U.S. trends in food availability and a dietary assessment of loss-adjusted food availability, 1970-2014. EIB-166, U.S. Department of Agriculture, Economic Research Service (2017).

  125. Martínez Steele, E. et al. Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study. BMJ Open 6, e009892 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Grant, B. F. et al. Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the United States, 2001–2002 to 2012–2013: results from the national epidemiologic survey on alcohol and related conditions. JAMA. Psychiatry 74, 911–923 (2017).

    Google Scholar 

  127. Chassaing, B., Van de Wiele, T., De Bodt, J., Marzorati, M. & Gewirtz, A. T. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut 66, 1414–1427 (2017).

    Article  CAS  PubMed  Google Scholar 

  128. Zmora, N., Bashiardes, S., Levy, M. & Elinav, E. The role of the immune system in metabolic health and disease. Cell Metab. 25, 506–521 (2017).

    Article  CAS  PubMed  Google Scholar 

  129. Richards, J. L., Yap, Y. A., McLeod, K. H., Mackay, C. R. & Mariño, E. Dietary metabolites and the gut microbiota: an alternative approach to control inflammatory and autoimmune diseases. Clin. Trans. Immunol. 5, e82 (2016).

    Article  CAS  Google Scholar 

  130. Bishehsari, F. et al. Alcohol and gut-derived inflammation. Alcohol Res. 38, 163–171 (2017).

    PubMed  PubMed Central  Google Scholar 

  131. Lerner, A. & Matthias, T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimm. Rev. 14, 479–489 (2015).

    Article  CAS  Google Scholar 

  132. Vlassara, H. & Striker, G. E. AGE restriction in diabetes mellitus: a paradigm shift. Nat. Rev. Endocrinol. 7, 526–539 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Dickinson, S., Hancock, D. P., Petocz, P., Ceriello, A. & Brand-Miller, J. High-glycemic index carbohydrate increases nuclear factor-kappaB activation in mononuclear cells of young, lean healthy subjects. Am. J. Clin. Nutr. 87, 1188–1193 (2008).

    CAS  PubMed  Google Scholar 

  134. Mozaffarian, D., Aro, A. & Willett, W. C. Health effects of trans-fatty acids: experimental and observational evidence. Eur. J. Clin. Nutr. 63, S5–S21 (2009).

    Article  CAS  PubMed  Google Scholar 

  135. Muller, D. N., Wilck, N., Haase, S., Kleinewietfeld, M. & Linker, R. A. Sodium in the microenvironment regulates immune responses and tissue homeostasis. Nat. Rev. Immunol. 19, 243–254 (2019).

    Article  PubMed  CAS  Google Scholar 

  136. Schnabel, L. et al. Association between ultraprocessed food consumption and risk of mortality among middle-aged adults in France. JAMA Intern. Med. 179, 490–498 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  137. Bonaventura, P., Benedetti, G., Albarède, F. & Miossec, P. Zinc and its role in immunity and inflammation. Autoimm. Rev. 14, 277–285 (2015).

    Article  CAS  Google Scholar 

  138. Nielsen, F. H. Effects of magnesium depletion on inflammation in chronic disease. Curr. Opin. Clin. Nutr. Metab. Care 17, 525–530 (2014).

    Article  CAS  PubMed  Google Scholar 

  139. Calder, P. C. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem. Soc. Trans. 45, 1105–1115 (2017).

    Article  CAS  PubMed  Google Scholar 

  140. Blasbalg, T. L., Hibbeln, J. R., Ramsden, C. E., Majchrzak, S. F. & Rawlings, R. R. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am. J. Clin. Nutr. 93, 950–962 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Calder, P. C. Very long-chain n-3 fatty acids and human health: fact, fiction and the future. Proc. Nutr. Soc. 77, 52–72 (2018).

    Article  CAS  PubMed  Google Scholar 

  142. Kiecolt-Glaser, J. K. et al. Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial. Brain Behav. Immun. 25, 1725–1734 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Kiecolt-Glaser, J. K. et al. Omega-3 supplementation lowers inflammation in healthy middle-aged and older adults: a randomized controlled trial. Brain Behav. Immun. 26, 988–995 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. AbuMweis, S., Jew, S., Tayyem, R. & Agraib, L. Eicosapentaenoic acid and docosahexaenoic acid containing supplements modulate risk factors for cardiovascular disease: a meta-analysis of randomised placebo-control human clinical trials. J. Hum. Nutr. Diet. 31, 67–84 (2017).

    Article  PubMed  Google Scholar 

  145. Danaei, G. et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med. 6, e1000058 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  146. GBD 2017 Diet Collaborators. Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 393, 1958–1972 (2019).

    Article  Google Scholar 

  147. Hall, K. D. Did the food environment cause theobesity epidemic? Obesity (Silver Spring) 26, 11–13 (2018).

    Article  Google Scholar 

  148. van Niekerk, G., Toit, du, A., Loos, B. & Engelbrecht, A.-M. Nutrient excess and autophagic deficiency: explaining metabolic diseases in obesity. Metab. Clin. Exp. 82, 14–21 (2018).

    Article  PubMed  CAS  Google Scholar 

  149. Slavich, G. M. & Irwin, M. R. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol. Bull. 140, 774–815 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  150. Tobaldini, E. et al. Short sleep duration and cardiometabolic risk: from pathophysiology to clinical evidence. Nat. Rev. Cardiol. 16, 213–224 (2019).

    Article  PubMed  Google Scholar 

  151. Reutrakul, S. & Van Cauter, E. Sleep influences on obesity, insulin resistance, and risk of type 2 diabetes. Metab. Clin. Exp. 84, 56–66 (2018).

    Article  CAS  PubMed  Google Scholar 

  152. Valtorta, N. K., Kanaan, M., Gilbody, S., Ronzi, S. & Hanratty, B. Loneliness and social isolation as risk factors for coronary heart disease and stroke: systematic review and meta-analysis of longitudinal observational studies. Heart 102, 1009–1016 (2016).

    Article  CAS  PubMed  Google Scholar 

  153. Steptoe, A., Shankar, A., Demakakos, P. & Wardle, J. Social isolation, loneliness, and all-cause mortality in older men and women. Proc. Natl Acad. Sci. USA 110, 5797–5801 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Kivimaki, M. & Steptoe, A. Effects of stress on the development and progression of cardiovascular disease. Nat. Rev. Cardiol. 15, 215–229 (2018).

    Article  CAS  PubMed  Google Scholar 

  155. Chandola, T., Brunner, E. & Marmot, M. Chronic stress at work and the metabolic syndrome: prospective study. BMJ 332, 521–525 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  156. Cohen, S. et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc. Natl Acad. Sci. USA 109, 5995–5999 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Lunn, R. M. et al. Health consequences of electric lighting practices in the modern world: a report on the National Toxicology Program’s workshop on shift work at night, artificial light at night, and circadian disruption. Sci. Total Environ. 607–608, 1073–1084 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Hatori, M. et al. Global rise of potential health hazards caused by blue light-induced circadian disruption in modern aging societies. NPJ Aging Mech. Dis. 3, 9 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  159. Touitou, Y., Reinberg, A. & Touitou, D. Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: health impacts and mechanisms of circadian disruption. Life Sci. 173, 94–106 (2017).

    Article  CAS  PubMed  Google Scholar 

  160. Leproult, R., Holmbäck, U. & Van Cauter, E. Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss. Diabetes 63, 1860–1869 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Jiang, C. et al. Dynamic human environmental exposome revealed by longitudinal personal monitoring. Cell 175, 277–291.e31 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Sly, P. D. et al. Health consequences of environmental exposures: causal thinking in global environmental epidemiology. Ann. Glob. Health 82, 3–9 (2016).

    Article  PubMed  Google Scholar 

  163. Collins, F. S., Gray, G. M. & Bucher, J. R. Toxicology. Transforming environmental health protection. Science 319, 906–907 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Kleinstreuer, N. C. et al. Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms. Nat. Biotechnol. 32, 583–591 (2014).

    Article  CAS  PubMed  Google Scholar 

  165. Thompson, P. A. et al. Environmental immune disruptors, inflammation and cancer risk. Carcinogenesis 36, S232–S253 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Floreani, A., Leung, P. S. C. & Gershwin, M. E. Environmental basis of autoimmunity. Clin. Rev. Allergy Immunol. 50, 287–300 (2016).

    Article  CAS  PubMed  Google Scholar 

  167. GBD 2015 Tobacco Collaborators. Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015: a systematic analysis from the Global Burden of Disease Study 2015. Lancet 389, 1885–1906 (2017).

    Article  Google Scholar 

  168. McDade, T. W., Rutherford, J., Adair, L. & Kuzawa, C. W. Early origins of inflammation: microbial exposures in infancy predict lower levels of C-reactive protein in adulthood. Proc. Biol. Sci. 277, 1129–1137 (2010).

    Article  CAS  PubMed  Google Scholar 

  169. Fagundes, C. P., Glaser, R. & Kiecolt-Glaser, J. K. Stressful early life experiences and immune dysregulation across the lifespan. Brain Behav. Immun. 27, 8–12 (2013).

    Article  CAS  PubMed  Google Scholar 

  170. Slavich, G. M., Way, B. M., Eisenberger, N. I. & Taylor, S. E. Neural sensitivity to social rejection is associated with inflammatory responses to social stress. Proc. Natl Acad. Sci. USA 107, 14817–14822 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Macpherson, A. J., de Agüero, M. G. & Ganal-Vonarburg, S. C. How nutrition and the maternal microbiota shape the neonatal immune system. Nat. Rev. Immunol. 17, 508–517 (2017).

    Article  CAS  PubMed  Google Scholar 

  172. Blazkova, J. et al. Multicenter systems analysis of human blood reveals immature neutrophils in males and during pregnancy. J. Immunol. 198, 2479–2488 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Aghaeepour, N. et al. An immune clock of human pregnancy. Sci. Immunol. 2, eaan2946 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  174. Simmen, F. A. & Simmen, R. C. M. The maternal womb: a novel target for cancer prevention in the era of the obesity pandemic? Eur. J. Cancer Prev. 20, 539–548 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Le Belle, J. E. et al. Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells. Stem Cell Reports 3, 725–734 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  176. Su, L. F. et al. The promised land of human immunology. Cold Spring Harb. Symp. Quant. Biol. 78, 203–213 (2013).

    Article  PubMed  Google Scholar 

  177. Davis, M. M., Tato, C. M. & Furman, D. Systems immunology: just getting started. Nat. Immunol. 18, 725–732 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Schüssler-Fiorenza Rose, S. M. et al. A longitudinal big data approach for precision health. Nat. Med. 25, 792–804 (2019).

    Article  PubMed  CAS  Google Scholar 

  179. Slavich, G. M. & Sacher, J. Stress, sex hormones, inflammation, and major depressive disorder: extending social signal transduction theory of depression to account for sex differences in mood disorders. Psychopharmacology (Berl.) 236, 3063–3079 (2019).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was made possible by support from the National Institutes of Health (NIH) and the Buck Institute for Research on Aging to D.F., the National Institute on Aging, Glenn and SENS Foundations, and the Buck Institute for Research on Aging to J.C.; the Ministry of Education and Science of the Russian Federation Agreement (074-02-2018-330) and Horizon 2020 Framework Programme (634821, PROPAG-AGING) and JPco-fuND (ADAGE) to C.F.; the Intramural Research Program of the National Institute of Aging, NIH to L.F.; the MRC (UK) and Wellcome Trust to D.W.G.; NIH grant (R01 DK104344) to A.F.; the European Research Commission (PHII-669415), Associazione Italiana Ricerca sul Cancro (Projects IG 19014, 5x1000 9962 and 21147), Fondazione Cariplo, and Italian Ministry of Health to A.M.; NIH grant (P01 AG036695) to T.A.R.; the National Institute on Aging and UCLA AIDS Institute to R.B.E.; the Spanish Ministry of Economy and Competitiveness and Fondos FEDER (PI15/00558 and PI18/00139) to A.L.; and a Society in Science–Branco Weiss Fellowship, NARSAD Young Investigator Grant 23958 from the Brain & Behavior Research Foundation and NIH grant (K08 MH103443) to G.M.S. This work represents the opinion of the authors and does not reflect official NIH policy.

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Authors and Affiliations

  1. Buck Institute for Research on Aging, Novato, CA, USA

    David Furman, Judith Campisi & Eric Verdin

  2. Stanford 1000 Immunomes Project, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA

    David Furman

  3. Institute for Research in Translational Medicine, Universidad Austral, CONICET, Pilar, Buenos Aires, Argentina

    David Furman

  4. Iuve Inc., San Mateo, CA, USA

    David Furman & Sasha Targ

  5. Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Judith Campisi

  6. Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital, Malmö, Sweden

    Pedro Carrera-Bastos

  7. Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USA

    Sasha Targ

  8. IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy

    Claudio Franceschi

  9. Department of Applied Mathematics and Laboratory of Systems Biology of Aging, Lobachevsky University, Nizhny Novgorod, Russia

    Claudio Franceschi

  10. Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA

    Luigi Ferrucci

  11. Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, University College London, London, UK

    Derek W. Gilroy

  12. MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, USA

    Alessio Fasano

  13. Department of Environmental Health Sciences, School of Public Health, Columbia University Medical Center, New York, NY, USA

    Gary W. Miller

  14. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

    Andrew H. Miller

  15. Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Alberto Mantovani

  16. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy

    Alberto Mantovani

  17. William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University, London, UK

    Alberto Mantovani

  18. Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA

    Cornelia M. Weyand

  19. Departments of Medicine and Genetics, Albert Einstein College of Medicine, New York, NY, USA

    Nir Barzilai

  20. Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA

    Jorg J. Goronzy & Thomas A. Rando

  21. Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA

    Thomas A. Rando

  22. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA

    Thomas A. Rando

  23. Department of Pathology, University of California, Los Angeles, Los Angeles, CA, USA

    Rita B. Effros

  24. Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain

    Alejandro Lucia

  25. Research Institute of the Hospital 12 de Octubre (i+12), Madrid, Spain

    Alejandro Lucia

  26. Biostatistics and Computational Biology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA

    Nicole Kleinstreuer

  27. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA

    Nicole Kleinstreuer

  28. Cousins Center for Psychoneuroimmunology and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA

    George M. Slavich

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Furman, D., Campisi, J., Verdin, E. et al. Chronic inflammation in the etiology of disease across the life span. Nat Med 25, 1822–1832 (2019). https://doi.org/10.1038/s41591-019-0675-0

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