Inflammaging in Endemic Areas for Infectious Diseases

Marina Andrade Batista1, Fernanda Calvo-Fortes1, Gabriela Silveira‐Nunes2, Giovanna Caliman Camatta1, Elaine Speziali3, Silvia Turroni4, Andréa Teixeira−Carvalho3, Olindo Assis Martins‐Filho3, Nicola Neretti5, Tatiani Uceli Maioli1, Rodrigo Ribeiro dos Santos6, Patrizia Brigidi4, Claudio Franceschi7,8, Ana Maria Caetano Faria9,1
1Programa de Pós Graduação em Nutrição e Saúde, Escola de Enfermagem, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
2Departamento de Medicina, Universidade Federal de Juiz de Fora, Governador Valadares, Brazil
3Instituto Rene Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil
4Unit of Microbial Ecology of Health, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
5Departament of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, United States
6Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
7Center for Biophysics, Bioinformatics, Biocomplexity, University of Bologna, Bologna, Italy
8Laboratory of Systems Biology of Healthy Aging, Department of Applied Mathematics, Lobachevsky University, Nizhny Novgorod, Russia
9Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

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Franceschi, 2000, The network and the remodeling theories of aging: Historical background and new perspectives, Exp Gerontol, 35, 10.1016/S0531-5565(00)00172-8

Franceschi, 2006, Inflamm-aging: An Evolutionary Perspective on Immunosenescence, Ann N Y Acad Sci, 908, 10.1111/j.1749-6632.2000.tb06651.x

Fulop, 2018, The integration of inflammaging in age-related diseases, Semin Immunol, 40, 17, 10.1016/j.smim.2018.09.003

Aiello, 2019, Immunosenescence and its hallmarks: How to oppose aging strategically? A review of potential options for therapeutic intervention, Front Immunol, 10, 10.3389/fimmu.2019.02247

Vasto, 2007, Inflammatory networks in ageing, age-related diseases and longevity, Mech Ageing Dev, 128, 83, 10.1016/j.mad.2006.11.015

Ferrucci, 2005, The origins of age-related proinflammatory state, Blood, 105, 10.1182/blood-2004-07-2599

World report on ageing and health1225LuxembourgWorld Health Organization Press2015

Nepomuceno, 2020, The Population of Centenarians in Brazil: Historical Estimates from 1900 to 2000, Popul Dev Rev, 46, 76, 10.1111/padr.12355

Ligthart, 1984, Admission criteria for immunogerontological studies in man: The senieur protocol, Mech Ageing Dev, 28, 47, 10.1016/0047-6374(84)90152-0

Rowe, 1987, Human aging: Usual and successful, Science (80- ), 237, 10.1126/science.3299702

Rowe, 2000, Successful aging and disease prevention, Adv Ren Replace Ther, 7, 10.1016/S1073-4449(00)70008-2

Castle, 2001, The SENIEUR protocol after 16 years: a need for a paradigm shift, Mech Ageing Dev, 122, 10.1016/S0047-6374(00)00240-2

Myśliwska, 1999, The upregulation of TNFα production is not a generalised phenomenon in the elderly between their sixth and seventh decades of life, Mech Ageing Dev, 107, 1, 10.1016/S0047-6374(98)00111-0

Wikby, 2002, The OCTO and NONA immune longitudinal studies: a review of 11 years studies of Swedish very old humans, Adv Cell Aging Gerontol, 13, 1, 10.1016/S1566-3124(02)13001-X

Nilsson, 2003, Morbidity does not influence the T-cell immune risk phenotype in the elderly: Findings in the Swedish NONA Immune Study using sample selection protocols, Mech Ageing Dev, 124, 10.1016/S0047-6374(03)00024-1

Evert, 2003, Morbidity Profiles of Centenarians: Survivors, Delayers, and Escapers, J Gerontol Ser A Biol Sci Med Sci, 58, 10.1093/gerona/58.3.M232

Franceschi, 2003, Centenarians as a model for healthy aging, Biochem Soc Trans, 31, 10.1042/bst0310457

Miller, 2001, New paradigms for research on aging and late-life illness, Mech Ageing Dev, 122, 10.1016/S0047-6374(00)00239-6

Dubois, 2016, Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria, Alzheimer’s Dement, 12, 292, 10.1016/j.jalz.2016.02.002

Htike, 2019, Peripheral Biomarkers for Early Detection of Alzheimer’s and Parkinson’s Diseases, Mol Neurobiol, 56, 10.1007/s12035-018-1151-4

Mondadori, 2006, Enhanced brain activity may precede the diagnosis of Alzheimer’s disease by 30 years, Brain, 129, 10.1093/brain/awl266

Kennedy, 2014, Geroscience: Linking Aging to Chronic Disease, Cell, 159, 10.1016/j.cell.2014.10.039

Franceschi, 1995, The immunology of exceptional individuals: the lesson of centenarians, Immunol Today, 16, 10.1016/0167-5699(95)80064-6

Cossarizza, 1997, Cytometric analysis of immunosenescence, Cytometry, 27, 297, 10.1002/(sici)1097-0320(19970401)27:4<297::aid-cyto1>3.0.co;2-a

Ferrucci, 2020, Measuring biological aging in humans: A quest, Aging Cell, 19, 1, 10.1111/acel.13080

Lanna, 2016, A new proposal for the clinical-functional categorization of the elderly: Visual Scale of Frailty (VS-Frailty), J Aging Res Clin Practice, 5, 24, 10.14283/jarcp.2016.84

Fried, 2001, Frailty in Older Adults: Evidence for a Phenotype, J Gerontol Ser A Biol Sci Med Sci, 56, 10.1093/gerona/56.3.M146

Franceschi, 2018, Inflammaging: a new immune–metabolic viewpoint for age-related diseases, Nat Rev Endocrinol, 14, 10.1038/s41574-018-0059-4

Thomas, 2020, Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging, Immun Ageing, 17, 2, 10.1186/s12979-020-0173-8

Goronzy, 2017, Successful and Maladaptive T Cell Aging, Immunity, 46, 10.1016/j.immuni.2017.03.010

Calcinotto, 2019, Cellular Senescence: Aging, Cancer, and Injury, Physiol Rev, 99, 10.1152/physrev.00020.2018

McElhaney, 2009, Immunosenescence: what does it mean to health outcomes in older adults, Curr Opin Immunol, 21, 10.1016/j.coi.2009.05.023

Xu, 2017, Markers of T Cell Senescence in Humans, Int J Mol Sci, 18, 10.3390/ijms18081742

Pawelec, 2019, Immune signatures associated with mortality differ in elderly populations from different birth cohorts and countries even within northern Europe, Mech Ageing Dev, 177, 10.1016/j.mad.2018.04.005

Franceschi, 2017, Immunobiography and the heterogeneity of immune responses in the elderly: A focus on inflammaging and trained immunity, Front Immunol, 8, 10.3389/fimmu.2017.00982

Bauer, 2016, The role of oxidative and inflammatory stress and persistent viral infections in immunosenescence, Mech Ageing Dev, 158, 27, 10.1016/j.mad.2016.01.001

Fagnoni, 2000, Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging, Blood, 95, 10.1182/blood.V95.9.2860.009k35_2860_2868

Cossarizza, 1996, CD45 isoforms expression on CD4+ and CD8+ T cells throughout life, from newborns to centenarians: implications for T cell memory, Mech Ageing Dev, 86, 10.1016/0047-6374(95)01691-0

Kovtonyuk, 2016, Inflamm-Aging of Hematopoiesis, Hematopoietic Stem Cells, and the Bone Marrow Microenvironment, Front Immunol, 7, 10.3389/fimmu.2016.00502

Lazuardi, 2005, Age-related loss of naive T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes, Immunology, 114, 37, 10.1111/j.1365-2567.2004.02006.x

Chambers, 2020, Can blocking inflammation enhance immunity during aging, J Allergy Clin Immunol, 145, 10.1016/j.jaci.2020.03.016

Fulop, 2018, Immunosenescence and inflamm-aging as two sides of the same coin: Friends or Foes, Front Immunol, 8, 10.3389/fimmu.2017.01960

Lehallier, 2019, Undulating changes in human plasma proteome profiles across the lifespan, Nat Med, 25, 10.1038/s41591-019-0673-2

Faria, 2014, Population Immunology: Germs, Aging and Inflammation, Eco-immunology, 10.1007/978-94-017-8712-3_8

De Martinis, 2005, Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity, FEBS Lett, 579, 10.1016/j.febslet.2005.02.055

Müller, 2013, Immunosenescence in vertebrates and invertebrates, Immun Ageing, 10, 10.1186/1742-4933-10-12

Grignolio, 2014, Towards a Liquid Self: How Time, Geography, and Life Experiences Reshape the Biological Identity, Front Immunol, 5, 10.3389/fimmu.2014.00153

De Martinis, 2004, Phenotypic and functional changes of circulating monocytes and polymorphonuclear leucocytes from elderly persons, Immunol Cell Biol, 82, 10.1111/j.0818-9641.2004.01242.x

Frei, 2012, Microbiota and dietary interactions - an update to the hygiene hypothesis, Allergy, 67, 10.1111/j.1398-9995.2011.02783.x

Pawelec, 2006, Immunity and ageing in man, Exp Gerontol, 41, 10.1016/j.exger.2006.09.005

Silveira-Nunes, 2017, Lifewide profile of cytokine production by innate and adaptive immune cells from Brazilian individuals, Immun Ageing, 14, 10.1186/s12979-017-0084-5

Weinberger, 2008, Biology of Immune Responses to Vaccines in Elderly Persons, Clin Infect Dis, 10.1086/529197

Baylis, 2013, Understanding how we age: insights into inflammaging, Longev Heal, 2, 10.1186/2046-2395-2-8

Montgomery, 2015, Paradoxical changes in innate immunity in aging: recent progress and new directions, J Leukoc Biol, 10.1189/jlb.5MR0315-104R

Solana, 2006, Aging and Innate Immunity, Immunity, 24, 10.1016/j.immuni.2006.05.003

Salminen, 2020, Activation of immunosuppressive network in the aging process, Ageing Res Rev, 57, 10.1016/j.arr.2019.100998

Le Garff-Tavernier, 2010, Human NK cells display major phenotypic and functional changes over the life span, Aging Cell, 9, 10.1111/j.1474-9726.2010.00584.x

Almeida-Oliveira, 2011, Age-related changes in natural killer cell receptors from childhood through old age, Hum Immunol, 72, 10.1016/j.humimm.2011.01.009

Kaszubowska, 2018, CD56bright cells respond to stimulation until very advanced age revealing increased expression of cellular protective proteins SIRT1, HSP70 and SOD2, Immun Ageing, 15, 31, 10.1186/s12979-018-0136-5

Franceschi, 2014, Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases, J Gerontol Ser A Biol Sci Med Sci, 69, 10.1093/gerona/glu057

Latz, 2018, NLRP3 inflammasome activation in inflammaging, Semin Immunol, 40, 61, 10.1016/j.smim.2018.09.001

Franceschi, 2007, Inflammaging as a Major Characteristic of Old People: Can It Be Prevented or Cured, Nutr Rev, 65, 10.1111/j.1753-4887.2007.tb00358.x

Franceschi, 2017, Inflammaging and ‘Garb-aging.’, Trends Endocrinol Metab, 28, 199, 10.1016/j.tem.2016.09.005

de Bourcy, 2017, Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging, Proc Natl Acad Sci, 114, 10.1073/pnas.1617959114

Ghosh, 2016, The Senescence-Associated Secretory Phenotype: Critical Effector in Skin Cancer and Aging, J Invest Dermatol, 136, 10.1016/j.jid.2016.06.621

Campisi, 2019, From discoveries in ageing research to therapeutics for healthy ageing, Nature, 571, 10.1038/s41586-019-1365-2

Furman, 2019, Chronic inflammation in the etiology of disease across the life span, Nat Med, 25, 10.1038/s41591-019-0675-0

Rea, 2018, Age and age-related diseases: Role of inflammation triggers and cytokines, Front Immunol, 9, 10.3389/fimmu.2018.00586

de Magalhães, 2018, Stress, cell senescence and organismal ageing, Mech Ageing Dev, 170, 2, 10.1016/j.mad.2017.07.001

Mensà, 2020, Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells, J Extracell Vesicles, 9, 10.1080/20013078.2020.1725285

Pawelec, 2001, The SENIEUR protocol after 16 years, Mech Ageing Dev, 122, 10.1016/S0047-6374(00)00240-2

Rubino, 2019, Sicilian centenarian offspring are more resistant to immune ageing, Aging Clin Exp Res, 31, 10.1007/s40520-018-0936-7

Amaral, 2010, Antigenic dietary protein guides maturation of the host immune system promoting resistance to Leishmania major infection in C57BL/6 mice, Immunology, 129, 10.1111/j.1365-2567.2009.03198.x

Lee, 2010, Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System, Science (80- ), 330, 10.1126/science.1195568

Lozupone, 2012, Diversity, stability and resilience of the human gut microbiota, Nature, 489, 10.1038/nature11550

Milani, 2017, The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota, Microbiol Mol Biol Rev, 81, 10.1128/MMBR.00036-17

Bokulich, 2016, Antibiotics, birth mode, and diet shape microbiome maturation during early life, Sci Transl Med, 8, 343ra82, 10.1126/scitranslmed.aad7121

Yassour, 2016, Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability, Sci Transl Med, 8, 343ra81, 10.1126/scitranslmed.aad0917

Yatsunenko, 2012, Human gut microbiome viewed across age and geography, Nature, 486, 10.1038/nature11053

Takiishi, 2017, Intestinal barrier and gut microbiota: Shaping our immune responses throughout life, Tissue Barriers, 5, e1373208, 10.1080/21688370.2017.1373208

Benveniste, 1971, Immunoglobulins in intact, immunized, and contaminated axenic mice: study of serum IgA, J Immunol, 107, 10.4049/jimmunol.107.6.1647

Hara, 2013, The role of the intestinal microbiota in type 1 diabetes, Clin Immunol, 146, 10.1016/j.clim.2012.12.001

Bauer, 1963, The response of the lymphatic tissue to the microbial flora. Studies on germfree mice, Am J Pathol, 42

Sommer, 2013, The gut microbiota — masters of host development and physiology, Nat Rev Microbiol, 11, 10.1038/nrmicro2974

Rajilić-Stojanović, 2007, Diversity of the human gastrointestinal tract microbiota revisited, Environ Microbiol, 9, 10.1111/j.1462-2920.2007.01369.x

Neish, 2009, Microbes in Gastrointestinal Health and Disease, Gastroenterology, 136, 65, 10.1053/j.gastro.2008.10.080

Ottaviani, 2011, Gut microbiota as a candidate for lifespan extension: an ecological/evolutionary perspective targeted on living organisms as metaorganisms, Biogerontology, 12, 599, 10.1007/s10522-011-9352-5

Candela, 2010, Functional intestinal microbiome, new frontiers in prebiotic design, Int J Food Microbiol, 140, 93, 10.1016/j.ijfoodmicro.2010.04.017

Silveira-Nunes, 2020, Hypertension Is Associated With Intestinal Microbiota Dysbiosis and Inflammation in a Brazilian Population, Front Pharmacol, 11, 10.3389/fphar.2020.00258

Turroni, 2020, The infant gut microbiome as a microbial organ influencing host well-being, Ital J Pediatr, 46, 16, 10.1186/s13052-020-0781-0

Rinninella, 2019, Food Components and Dietary Habits: Keys for a Healthy Gut Microbiota Composition, Nutrients, 11, 10.3390/nu11102393

Marchesi, 2016, The gut microbiota and host health: a new clinical frontier, Gut, 65, 10.1136/gutjnl-2015-309990

da Silva Menezes, 2003, Stimulation by food proteins plays a critical role in the maturation of the immune system, Int Immunol, 15, 10.1093/intimm/dxg043

Duchmann, 1997, Responses to self and non-self intestinal microflora in health and inflammatory bowel disease, Res Immunol, 148, 10.1016/S0923-2494(98)80154-5

Faria, 2006, Oral Tolerance: Therapeutic Implications for Autoimmune Diseases, Clin Dev Immunol, 13, 10.1080/17402520600876804

Izcue, 2006, Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation, Immunol Rev, 212, 10.1111/j.0105-2896.2006.00423.x

Claesson, 2012, Gut microbiota composition correlates with diet and health in the elderly, Nature, 488, 10.1038/nature11319

Biagi, 2010, Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians, PLoS One, 5, e10667, 10.1371/journal.pone.0010667

O’Toole, 2018, Microbiome–health interactions in older people, Cell Mol Life Sci, 75, 10.1007/s00018-017-2673-z

Biagi, 2016, Gut Microbiota and Extreme Longevity, Curr Biol, 26, 10.1016/j.cub.2016.04.016

Rampelli, 2020, Shotgun Metagenomics of Gut Microbiota in Humans with up to Extreme Longevity and the Increasing Role of Xenobiotic Degradation, mSystems, 5, 10.1128/mSystems.00124-20

Cummings, 1987, Short chain fatty acids in human large intestine, portal, hepatic and venous blood, Gut, 28, 10.1136/gut.28.10.1221

Vinolo, 2011, Regulation of inflammation by short chain fatty acids, Nutrients, 3, 10.3390/nu3100858

Usami, 2008, Butyrate and trichostatin A attenuate nuclear factor κB activation and tumor necrosis factor α secretion and increase prostaglandin E2 secretion in human peripheral blood mononuclear cells, Nutr Res, 28, 10.1016/j.nutres.2008.02.012

Ivanov, 2010, Segmented filamentous bacteria take the stage, Mucosal Immunol, 3, 10.1038/mi.2010.3

Rooks, 2016, Gut microbiota, metabolites and host immunity, Nat Rev Immunol, 16, 10.1038/nri.2016.42

Biesalski, 2016, Nutrition meets the microbiome: micronutrients and the microbiota, Ann N Y Acad Sci, 1372, 53, 10.1111/nyas.13145

Magnúsdóttir, 2015, Systematic genome assessment of B-vitamin biosynthesis suggests cooperation among gut microbes, Front Genet, 6, 10.3389/fgene.2015.00148

Choi, 2018, Zinc deficiency and cellular oxidative stress: prognostic implications in cardiovascular diseases, Acta Pharmacol Sin, 39, 10.1038/aps.2018.25

Chasapis, 2020, Recent aspects of the effects of zinc on human health, Arch Toxicol, 94, 10.1007/s00204-020-02702-9

Gammoh, 2017, Zinc in infection and inflammation, Nutrients, 9, 10.3390/nu9060624

Wong, 2012, Zinc and its role in age-related inflammation and immune dysfunction, Mol Nutr Food Res, 56, 77, 10.1002/mnfr.201100511

Miranda, 2018, High salt diet exacerbates colitis in mice by decreasing Lactobacillus levels and butyrate production, Microbiome, 6, 57, 10.1186/s40168-018-0433-4

Aguiar, 2018, High-salt diet induces IL-17-dependent gut inflammation and exacerbates colitis in mice, Front Immunol, 8, 10.3389/fimmu.2017.01969

Franceschi, 2000, Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space, Vaccine, 18, 10.1016/S0264-410X(99)00513-7

Strachan, 1989, Hay fever, hygiene, and household size, BMJ, 299, 10.1136/bmj.299.6710.1259

Bloomfield, 2016, Time to abandon the hygiene hypothesis: New perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene, Perspect Public Health, 136, 10.1177/1757913916650225

Fasano, 2020, All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases, F1000Research, 9, 10.12688/f1000research.20510.1

Bach, 2018, The hygiene hypothesis in autoimmunity: The role of pathogens and commensals, Nat Rev Immunol, 18, 10.1038/nri.2017.111

Alexandre-Silva, 2018, The hygiene hypothesis at a glance: Early exposures, immune mechanism and novel therapies, Acta Trop, 188, 16, 10.1016/j.actatropica.2018.08.032

Bach, 2002, The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases, N Engl J Med, 347, 10.1056/NEJMra020100

Rook, 2012, Hygiene Hypothesis and Autoimmune Diseases, Clin Rev Allergy Immunol, 42, 5, 10.1007/s12016-011-8285-8

Feldman, 2015, Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma, Am J Respir Crit Care Med, 191, 34, 10.1164/rccm.201405-0901PP

Haspeslagh, 2018, The hygiene hypothesis: immunological mechanisms of airway tolerance, Curr Opin Immunol, 54, 10.1016/j.coi.2018.06.007

Gao, 2019, Critical roles of regulatory B and T cells in helminth parasite-induced protection against allergic airway inflammation, Clin Exp Immunol, 198, 390, 10.1111/cei.13362

Bach, 2012, The Hygiene Hypothesis: An Explanation for the Increased Frequency of Insulin-Dependent Diabetes, Cold Spring Harb Perspect Med, 2, 10.1101/cshperspect.a007799

Briggs, 2016, The Hygiene Hypothesis and Its Inconvenient Truths about Helminth Infections, PLoS Negl Trop Dis, 10, e0004944, 10.1371/journal.pntd.0004944

Burrows, 2015, Microbiota regulates type 1 diabetes through Toll-like receptors, Proc Natl Acad Sci, 112, 10.1073/pnas.1508740112

Sitcharungsi, 2013, Allergic diseases and helminth infections, Pathog Glob Health, 107, 10.1179/2047773213Y.0000000080

Ginaldi, 2005, Chronic antigenic load and apoptosis in immunosenescence, Trends Immunol, 26, 79, 10.1016/j.it.2004.11.005

Austad, 2018, Is antagonistic pleiotropy ubiquitous in aging biology, Evol Med Public Heal, 2018, 10.1093/emph/eoy033

Borras, 2020, Centenarians: An excellent example of resilience for successful ageing, Mech Ageing Dev, 186, 10.1016/j.mad.2019.111199

Gravina, 2009, Identification of single nucleotide polymorphisms in the p21 (CDKN1A) gene and correlations with longevity in the Italian population, Aging (Albany NY), 1, 10.18632/aging.100041

Franceschi, 2007, Genetics of healthy aging in Europe: The EU-integrated project GEHA (GEnetics of Healthy Aging), Ann N Y Acad Sci, 21

Perls, 2002, The genetics of exceptional human longevity, J Mol Neurosci, 19, 10.1007/s12031-002-0039-x

Giuliani, 2018, Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework, Circ Res, 123, 10.1161/CIRCRESAHA.118.312562

Unnikrishnan, 2019, The role of DNA methylation in epigenetics of aging, Pharmacol Ther, 195, 10.1016/j.pharmthera.2018.11.001

Tan, 2016, Epigenetic drift in the aging genome: A ten-year follow-up in an elderly twin cohort, Int J Epidemiol, 45, 10.1093/ije/dyw132

Bjornsson, 2008, Intra-individual Change Over Time in DNA Methylation With Familial Clustering, JAMA, 299, 10.1001/jama.299.24.2877

Sheldon, 1995, Age-related neoplasia in a lifetime study of ad libitum-fed and food- restricted B6C3F1 mice, Toxicol Pathol, 23, 10.1177/019262339502300403

Redman, 2018, Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging, Cell Metab, 27, 805, 10.1016/j.cmet.2018.02.019

Bowman, 2019, Obesity and Longer Term Risks of Dementia in 65-74 Year Olds, Age Ageing, 48, 10.1093/ageing/afz002

Liu, 2019, Telomere length and associated factors in older adults with hypertension, J Int Med Res, 47, 10.1177/0300060519882570

Cherkas, 2008, The association between physical activity in leisure time and leukocyte telomere length, Arch Intern Med, 168, 10.1001/archinternmed.2007.39

White, 2019, Shift work, DNA methylation and epigenetic age, Int J Epidemiol, 48, 10.1093/ije/dyz027

Andrews, 2009, Uncoupling protein-2 regulates lifespan in mice, Am J Physiol - Endocrinol Metab, 296, 10.1152/ajpendo.90903.2008

Guarente, 2005, Calorie restriction - The SIR2 connection, Cell, 120, 10.1016/j.cell.2005.01.029

Lescai, 2009, Human longevity and 11p15.5: A study in 1321 centenarians, Eur J Hum Genet, 17, 10.1038/ejhg.2009.54

Owczarz, 2017, miR-34a and miR-9 are overexpressed and SIRT genes are downregulated in peripheral blood mononuclear cells of aging humans, Exp Biol Med, 242, 10.1177/1535370217720884

Wu, 2020, Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls, Alzheimers Res Ther, 12, 1, 10.1186/s13195-020-00627-0

Elsharawy, 2012, Genome-wide miRNA signatures of human longevity, Aging Cell, 11, 10.1111/j.1474-9726.2012.00824.x

Carrieri, 2004, The G/C915 polymorphism of transforming growth factor β1 is associated with human longevity: A study in Italian centenarians, Aging Cell, 3, 10.1111/j.1474-9728.2004.00129.x

Olivieri, 2007, ApoE ϵ2/ϵ3/ϵ4 polymorphism, ApoC-III/ApoE ratio and metabolic syndrome, Clin Exp Med, 7, 10.1007/s10238-007-0142-y

Bae, 2018, Effects of FOXO3 Polymorphisms on Survival to Extreme Longevity in Four Centenarian Studies, J Gerontol - Ser A Biol Sci Med Sci, 73, 10.1093/gerona/glx124

de Oliveira, 2020, Selected LDLR and APOE Polymorphisms Affect Cognitive and Functional Response to Lipophilic Statins in Alzheimer’s Disease, J Mol Neurosci, 70, 10.1007/s12031-020-01588-7

Bessi, 2020, Influence of ApoE Genotype and Clock T3111C Interaction with Cardiovascular Risk Factors on the Progression to Alzheimer’s Disease in Subjective Cognitive Decline and Mild Cognitive Impairment Patients, J Pers Med, 10, 10.3390/jpm10020045

Dato, 2007, Genes and longevity: A genetic-demographic approach reveals sex- and age-specific gene effects not shown by the case-control approach (APOE and HSP70.1 loci), Biogerontology, 8, 31, 10.1007/s10522-006-9030-1

Andreasen, 2008, Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation, Diabetes, 57, 95, 10.2337/db07-0910

Keller, 2011, The obesity related gene, FTO, interacts with APOE, and is associated with Alzheimer’s disease risk: A prospective cohort study, J Alzheimer’s Dis, 23, 10.3233/JAD-2010-101068

Hirayama, 2020, FTO Demethylates Cyclin D1 mRNA and Controls Cell-Cycle Progression, Cell Rep, 31, 107464, 10.1016/j.celrep.2020.03.028

Rose, 2015, Metabolism and successful aging: Polymorphic variation of syndecan-4 (SDC4) gene associate with longevity and lipid profile in healthy elderly Italian subjects, Mech Ageing Dev, 150, 27, 10.1016/j.mad.2015.08.003

Melzer, 2020, The genetics of human ageing, Nat Rev Genet, 21, 88, 10.1038/s41576-019-0183-6

Mora, 2011, Aging phenotype and its relationship with IGF-I gene promoter polymorphisms in elderly people living in Catalonia, Growth Horm IGF Res, 21, 10.1016/j.ghir.2011.03.007

De Benedictis, 2006, The unusual genetics of human longevity, Sci Aging Knowledge Environ, 2006, pe20, 10.1126/sageke.2006.10.pe20

Solana, 2000, NK and NK/T cells in human senescence, Vaccine, 18, 10.1016/S0264-410X(99)00495-8

Di Bona, 2009, Effect of interleukin-6 polymorphisms on human longevity: A systematic review and meta-analysis, Ageing Res Rev, 8, 36, 10.1016/j.arr.2008.09.001

Sansoni, 2008, The immune system in extreme longevity, Exp Gerontol, 43, 10.1016/j.exger.2007.06.008

Goronzy, 2012, Signaling pathways in aged T cells-a reflection of T cell differentiation, cell senescence and host environment, Semin Immunol, 24, 10.1016/j.smim.2012.04.003

Lima-Costa, 2017, Predictive value of multiple cytokines and chemokines for mortality in an admixed population: 15-year follow-up of the Bambui-Epigen (Brazil) cohort study of aging, Exp Gerontol, 98, 47, 10.1016/j.exger.2017.08.002

Torres, 2018, Immune senescence and biomarkers profile of Bambuí aged population-based cohort, Exp Gerontol, 103, 47, 10.1016/j.exger.2017.12.006

Gavazzi, 2004, Aging and Infectious Diseases in the Developing World, Clin Infect Dis, 39, 83, 10.1086/421559

Coura, 2015, The main sceneries of chagas disease transmission. The vectors, blood and oral transmissions - A comprehensive review, Mem Inst Oswaldo Cruz, 110, 10.1590/0074-0276140362

Nunes, 2018, Chagas Cardiomyopathy: An Update of Current Clinical Knowledge and Management: A Scientific Statement From the American Heart Association, Circulation, 138, 10.1161/CIR.0000000000000599

Ferreira Bellini, 2012, Biologic and Genetics Aspects of Chagas Disease at Endemic Areas, J Trop Med, 2012, 10.1155/2012/357948

De Araújo, 2020, CXCL9 and CXCL10 display an age-dependent profile in Chagas patients: A cohort study of aging in Bambui, Brazil, Infect Dis Poverty, 9, 1, 10.1186/s40249-020-00663-w

Pagliano, 2017, Visceral leishmaniosis in immunocompromised host: an update and literature review, J Chemother, 29, 10.1080/1120009X.2017.1323150

2019, Situação Epidemiológica da Leishmaniose Visceral, Bol Epidemiológico Ministério da Saúde

Lindoso, 2018, Visceral leishmaniasis and HIV coinfection: Current perspectives, HIV/AIDS - Res Palliat Care, 10, 193, 10.2147/HIV.S143929

Hernandez-Perez, 1999, Visceral Leishmaniasis (Kala-azar) in Solid Organ Transplantation: Report of Five Cases and Review, Clin Infect Dis, 29, 10.1086/520457

Werneck, 2002, The burden of Leishmania chagasi infection during an urban outbreak of visceral leishmaniasis in Brazil, Acta Trop, 83, 10.1016/S0001-706X(02)00058-X

Douek, 2000, Effect of HIV on Thymic Function before and after Antiretroviral Therapy in Children, J Infect Dis, 181, 10.1086/315398

Appay, 2007, Accelerated immune senescence and HIV-1 infection, Exp Gerontol, 42, 10.1016/j.exger.2006.12.003

Sokoya, 2017, HIV as a Cause of Immune Activation and Immunosenescence, Mediators Inflamm, 2017, 10.1155/2017/6825493

Silva-Freitas, 2020, Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients, Front Immunol, 11, 10.3389/fimmu.2020.00953

Vos, 2012, Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010, Lancet, 380, 10.1016/S0140-6736(12)61729-2

Hay, 2017, Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016, Lancet, 390, 10.1016/S0140-6736(17)32130-X

Speziali, 2004, Production of interferon-γ by natural killer cells and aging in chronic human schistosomiasis, Mediators Inflamm, 13, 10.1080/09629350400008802

Comin, 2007, Ageing and Toll-like receptor expression by innate immune cells in chronic human schistosomiasis, Clin Exp Immunol, 149, 10.1111/j.1365-2249.2007.03403.x

Comin, 2008, Aging and immune response in chronic human schistosomiasis, Acta Trop, 108, 10.1016/j.actatropica.2008.05.004

Franceschi, 2018, The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates, Front Med, 5, 10.3389/fmed.2018.00061

Franceschi, 2018, Inflammaging 2018: An update and a model, Semin Immunol, 40, 1, 10.1016/j.smim.2018.10.008

Njemini, 2003, The induction of heat shock protein 70 in peripheral mononuclear blood cells in elderly patients: a role for inflammatory markers, Hum Immunol, 64, 10.1016/S0198-8859(03)00068-5

MacNee, 2016, Is Chronic Obstructive Pulmonary Disease an Accelerated Aging Disease, Ann Am Thorac Soc, 13, 10.1513/AnnalsATS.201602-124AW

Hurria, 2016, Cancer Treatment as an Accelerated Aging Process: Assessment, Biomarkers, and Interventions, Am Soc Clin Oncol Educ B, 10.1200/EDBK_156160

Levine, 2016, Menopause accelerates biological aging, Proc Natl Acad Sci, 113, 10.1073/pnas.1604558113

Bacalini, 2015, Identification of a DNA methylation signature in blood cells from persons with Down Syndrome, Aging (Albany NY), 7, 82, 10.18632/aging.100715

Biagi, 2014, Gut Microbiome in Down Syndrome, PLoS One, 9, e112023, 10.1371/journal.pone.0112023

Cohen, 2017, HIV-associated cellular senescence: A contributor to accelerated aging, Ageing Res Rev, 36, 10.1016/j.arr.2016.12.004

Dowd, 2009, Socioeconomic disparities in the seroprevalence of cytomegalovirus infection in the US population: NHANES III, Epidemiol Infect, 137, 58, 10.1017/S0950268808000551

Lachmann, 2018, Cytomegalovirus (CMV) seroprevalence in the adult population of Germany, PLoS One, 13, e0200267, 10.1371/journal.pone.0200267

Kadambari, 2020, Why the elderly appear to be more severely affected by COVID -19: The potential role of immunosenescence and CMV, Rev Med Virol, 30, e2144, 10.1002/rmv.2144

Al Mana, 2019, The Current Status of Cytomegalovirus (CMV) Prevalence in the MENA Region: A Systematic Review, Pathogens, 8, 10.3390/pathogens8040213

Klenerman, 2016, T cell responses to cytomegalovirus, Nat Rev Immunol, 16, 10.1038/nri.2016.38

Solana, 2012, CMV and Immunosenescence: from basics to clinics, Immun Ageing, 9, 10.1186/1742-4933-9-23

Vaes, 2010, The BELFRAIL (BFC80+) study: a population-based prospective cohort study of the very elderly in Belgium, BMC Geriatr, 10, 10.1186/1471-2318-10-39

Heath, 2020, The Immune Response Against Human Cytomegalovirus Links Cellular to Systemic Senescence, Cells, 9, 10.3390/cells9030766

Fülöp, 2013, Human T Cell Aging and the Impact of Persistent Viral Infections, Front Immunol, 4, 10.3389/fimmu.2013.00271

Strandberg, 2009, Cytomegalovirus Antibody Level and Mortality Among Community-Dwelling Older Adults With Stable Cardiovascular Disease, JAMA, 301, 10.1001/jama.2009.4

Simanek, 2011, Seropositivity to Cytomegalovirus, Inflammation, All-Cause and Cardiovascular Disease-Related Mortality in the United States, PLoS One, 6, e16103, 10.1371/journal.pone.0016103

Savva, 2013, Cytomegalovirus infection is associated with increased mortality in the older population, Aging Cell, 12, 10.1111/acel.12059

Bolovan-Fritts, 2008, Endothelial damage from cytomegalovirus-specific host immune response can be prevented by targeted disruption of fractalkine-CX3CR1 interaction, Blood, 111, 10.1182/blood-2007-08-107730

Pachnio, 2016, Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium, PLoS Pathog, 12, e1005832, 10.1371/journal.ppat.1005832

Bano, 2019, CD28null CD4 T-cell expansions in autoimmune disease suggest a link with cytomegalovirus infection, F1000Research, 8, 327, 10.12688/f1000research.17119.1

Pera, 2018, CD28 null pro-atherogenic CD4 T-cells explain the link between CMV infection and an increased risk of cardiovascular death, Theranostics, 8, 10.7150/thno.27428

Broadley, 2017, Expansions of Cytotoxic CD4+CD28– T Cells Drive Excess Cardiovascular Mortality in Rheumatoid Arthritis and Other Chronic Inflammatory Conditions and Are Triggered by CMV Infection, Front Immunol, 8, 10.3389/fimmu.2017.00195

Moss, 2020, “The ancient and the new”: is there an interaction between cytomegalovirus and SARS-CoV-2 infection, Immun Ageing, 17, 14, 10.1186/s12979-020-00185-x

Bajwa, 2016, Functional Diversity of Cytomegalovirus–Specific T Cells Is Maintained in Older People and Significantly Associated With Protein Specificity and Response Size, J Infect Dis, 214, 10.1093/infdis/jiw371

Terrazzini, 2014, A Novel Cytomegalovirus-Induced Regulatory-Type T-Cell Subset Increases in Size During Older Life and Links Virus-Specific Immunity to Vascular Pathology, J Infect Dis, 209, 10.1093/infdis/jit576

Jergović, 2019, Impact of CMV upon immune aging: facts and fiction, Med Microbiol Immunol, 208, 10.1007/s00430-019-00605-w

Moss, 2019, ‘From immunosenescence to immune modulation’: a re-appraisal of the role of cytomegalovirus as major regulator of human immune function, Med Microbiol Immunol, 208, 10.1007/s00430-019-00612-x

Furman, 2015, Cytomegalovirus infection enhances the immune response to influenza, Sci Transl Med, 7, 281ra43, 10.1126/scitranslmed.aaa2293

Merani, 2017, Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection, Front Immunol, 8, 10.3389/fimmu.2017.00784

Pawelec, 2011, Role of CMV in immune senescence, Virus Res, 157, 10.1016/j.virusres.2010.09.010

Pawelec, 2012, The impact of CMV infection on survival in older humans, Curr Opin Immunol, 24, 10.1016/j.coi.2012.04.002

Horvath, 2018, DNA methylation-based biomarkers and the epigenetic clock theory of ageing, Nat Rev Genet, 19, 10.1038/s41576-018-0004-3

Wu, 2020, Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China, JAMA Intern Med, 180, 10.1001/jamainternmed.2020.0994

Grasselli, 2020, Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy, JAMA, 323, 10.1001/jama.2020.5394

Aviv, 2020, Telomeres and COVID-19, FASEB J, 34, 10.1096/fj.202001025

Lauc, 2020, Biomarkers of biological age as predictors of COVID-19 disease severity, Aging (Albany NY), 12, 10.18632/aging.103052

Brooke, 2020, Reversing immunosenescence for prevention of COVID-19, Aging (Albany NY), 12, 10.18632/aging.103636