{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:01:20Z","timestamp":1792119680166,"version":"4.4.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,12,15]],"date-time":"2019-12-15T00:00:00Z","timestamp":1576368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","award":["HEALTH-F4-2008-200880 MARK-AGE"],"award-info":[{"award-number":["HEALTH-F4-2008-200880 MARK-AGE"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007514","name":"Universit\u00e0 di Pisa","doi-asserted-by":"publisher","award":["PRA_2017_38"],"award-info":[{"award-number":["PRA_2017_38"]}],"id":[{"id":"10.13039\/501100007514","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007514","name":"Universit\u00e0 di Pisa","doi-asserted-by":"publisher","award":["n.\u00a083\/2017"],"award-info":[{"award-number":["n.\u00a083\/2017"]}],"id":[{"id":"10.13039\/501100007514","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Torquetenovirus (TTV) viremia has been associated with increased mortality risk in the elderly population. This work aims to investigate TTV viremia as a potential biomarker of immunosenescence. We compared levels of circulating TTV in 1813 participants of the MARK-AGE project, including human models of delayed (offspring of centenarians [GO]) and premature (Down syndrome [DS]) immunosenescence. The TTV load was positively associated with age, cytomegalovirus (CMV) antibody levels, and the Cu\/Zn ratio and negatively associated with platelets, total cholesterol, and total IgM. TTV viremia was highest in DS and lowest in GO, with intermediate levels in the SGO (spouses of GO) and RASIG (Randomly Recruited Age-Stratified Individuals From The General Population) populations. In the RASIG population, TTV DNA loads showed a slight negative association with CD3+T-cells and CD4+T-cells. Finally, males with \u22654log TTV copies\/mL had a higher risk of having a CD4\/CD8 ratio&amp;lt;1 than those with lower viremia (odds ratio [OR] = 2.85, 95% confidence interval [CI]: 1.06\u20137.62), as well as reduced CD3+ and CD4+T-cells compared to males with lower replication rates (&amp;lt;4log), even after adjusting for CMV infection. In summary, differences in immune system preservation are reflected in the models of delayed and premature immunosenescence, displaying the best and worst control over TTV replication, respectively. In the general population, TTV loads were negatively associated with CD4+ cell counts, with an increased predisposition for an inverted CD4\/CD8 ratio for individuals with TTV loads \u22654log copies\/mL, thus promoting an immune risk phenotype.<\/jats:p>","DOI":"10.1093\/gerona\/glz293","type":"journal-article","created":{"date-parts":[[2019,12,15]],"date-time":"2019-12-15T08:37:21Z","timestamp":1576399041000},"page":"1838-1845","source":"Crossref","is-referenced-by-count":29,"title":["Prevalence and Loads of Torquetenovirus in the European MARK-AGE Study Population"],"prefix":"10.1093","volume":"75","author":[{"given":"Robertina","family":"Giacconi","sequence":"first","affiliation":[{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Maggi","sequence":"additional","affiliation":[{"name":"Department of Translational Research, University of Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Macera","sequence":"additional","affiliation":[{"name":"Department of Translational Research, University of Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro Giorgio","family":"Spezia","sequence":"additional","affiliation":[{"name":"Department of Translational Research, University of Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Pistello","sequence":"additional","affiliation":[{"name":"Department of Translational Research, University of Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Provinciali","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Piacenza","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Basso","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"B\u00fcrkle","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Group, Department of Biology, Box 628, University of Konstanz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Moreno-Villanueva","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Group, Department of Biology, Box 628, University of Konstanz, Germany"},{"name":"Human Performance Research Centre, Department of Sport Science, Box 30, University of Konstanz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn E T","family":"Doll\u00e9","sequence":"additional","affiliation":[{"name":"Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eug\u00e8ne","family":"Jansen","sequence":"additional","affiliation":[{"name":"Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Grune","sequence":"additional","affiliation":[{"name":"Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany"},{"name":"NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Stuetz","sequence":"additional","affiliation":[{"name":"Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstathios S","family":"Gonos","sequence":"additional","affiliation":[{"name":"National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Sch\u00f6n","sequence":"additional","affiliation":[{"name":"BioTeSys GmbH, Esslingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"BioTeSys GmbH, Esslingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrix","family":"Grubeck-Loebenstein","sequence":"additional","affiliation":[{"name":"Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Sikora","sequence":"additional","affiliation":[{"name":"Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Dudkowska","sequence":"additional","affiliation":[{"name":"Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Janiszewska","sequence":"additional","affiliation":[{"name":"Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Toussaint","sequence":"additional","affiliation":[{"name":"URBC-NARILIS, University of Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Debacq-Chainiaux","sequence":"additional","affiliation":[{"name":"URBC-NARILIS, University of Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Franceschi","sequence":"additional","affiliation":[{"name":"CIG-Interdepartmental Center \u201cL. Galvani,\u201d Alma Mater Studiorum, University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Capri","sequence":"additional","affiliation":[{"name":"CIG-Interdepartmental Center \u201cL. Galvani,\u201d Alma Mater Studiorum, University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Hervonen","sequence":"additional","affiliation":[{"name":"Medical School, University of Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"Hurme","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biosciences, University of Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Slagboom","sequence":"additional","affiliation":[{"name":"Department of Molecular Epidemiology, Leiden University Medical Centre, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolle","family":"Breusing","sequence":"additional","affiliation":[{"name":"Department of Applied Nutritional Science\/Dietetics, Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Mocchegiani","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Malavolta","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,15]]},"reference":[{"key":"2020092513345167000_CIT0001","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.cmi.2016.04.007","article-title":"Torquetenovirus: the human virome from bench to bedside","volume":"22","author":"Focosi","year":"2016","journal-title":"Clin Microbiol Infect"},{"key":"2020092513345167000_CIT0002","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.exger.2018.09.003","article-title":"Torquetenovirus (TTV) load is associated with mortality in Italian elderly subjects","volume":"112","author":"Giacconi","year":"2018","journal-title":"Exp Gerontol"},{"key":"2020092513345167000_CIT0003","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00430-017-0511-4","article-title":"Dynamics of Torque Teno virus viremia could predict risk of complications after allogeneic hematopoietic stem cell transplantation","volume":"206","author":"Gilles","year":"2017","journal-title":"Med Microbiol Immunol"},{"key":"2020092513345167000_CIT0004","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jcv.2018.09.014","article-title":"Virome definition in cerebrospinal fluid of patients with neurological complications after hematopoietic stem cell transplantation","volume":"108","author":"Pou","year":"2018","journal-title":"J Clin Virol"},{"key":"2020092513345167000_CIT0005","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1086\/444389","article-title":"Associations between nasal torquetenovirus load and spirometric indices in children with asthma","volume":"192","author":"Pifferi","year":"2005","journal-title":"J Infect Dis"},{"key":"2020092513345167000_CIT0006","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.virol.2009.08.036","article-title":"Torquetenovirus DNA drives proinflammatory cytokines production and secretion by immune cells via toll-like receptor 9","volume":"394","author":"Rocchi","year":"2009","journal-title":"Virology"},{"key":"2020092513345167000_CIT0007","doi-asserted-by":"crossref","first-page":"9716","DOI":"10.1007\/s11357-014-9716-2","article-title":"TTV DNA plasma load and its association with age, gender, and HCMV IgG serostatus in healthy adults","volume":"36","author":"Haloschan","year":"2014","journal-title":"Age (Dordr)"},{"key":"2020092513345167000_CIT0008","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s10522-015-9563-2","article-title":"Impact of age, sex and CMV-infection on peripheral T cell phenotypes: results from the Berlin BASE-II Study","volume":"16","author":"Di Benedetto","year":"2015","journal-title":"Biogerontology"},{"key":"2020092513345167000_CIT0009","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.coi.2012.04.002","article-title":"The impact of CMV infection on survival in older humans","volume":"24","author":"Pawelec","year":"2012","journal-title":"Curr Opin Immunol"},{"key":"2020092513345167000_CIT0010","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.maturitas.2015.05.004","article-title":"Immunosenescence: implications for response to infection and vaccination in older people","volume":"82","author":"Pera","year":"2015","journal-title":"Maturitas"},{"key":"2020092513345167000_CIT0011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exger.2013.11.010","article-title":"Immunosenenescence: role of cytomegalovirus","volume":"54","author":"Pawelec","year":"2014","journal-title":"Exp Gerontol"},{"key":"2020092513345167000_CIT0012","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/infdis\/jix255","article-title":"Persistent herpesvirus infections and telomere attrition over 3 years in the whitehall II cohort","volume":"216","author":"Dowd","year":"2017","journal-title":"J Infect Dis"},{"key":"2020092513345167000_CIT0013","doi-asserted-by":"crossref","first-page":"e16103","DOI":"10.1371\/journal.pone.0016103","article-title":"Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States","volume":"6","author":"Simanek","year":"2011","journal-title":"PLoS One"},{"key":"2020092513345167000_CIT0014","doi-asserted-by":"crossref","first-page":"e96779","DOI":"10.1371\/journal.pone.0096779","article-title":"Increased inflammatory response in cytomegalovirus seropositive patients with Alzheimer\u2019s disease","volume":"9","author":"Westman","year":"2014","journal-title":"PLoS One"},{"key":"2020092513345167000_CIT0015","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1007\/s11357-012-9400-3","article-title":"The inverted CD4\/CD8 ratio and associated parameters in 66-year-old individuals: the Swedish HEXA immune study","volume":"35","author":"Strindhall","year":"2013","journal-title":"Age (Dordr)"},{"key":"2020092513345167000_CIT0016","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.exger.2017.03.020","article-title":"CD4\/CD8 ratio","volume":"95","author":"Strindhall","year":"2017","journal-title":"Exp Gerontol"},{"key":"2020092513345167000_CIT0017","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s10522-008-9138-6","article-title":"The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20-100 years of age","volume":"9","author":"Wikby","year":"2008","journal-title":"Biogerontology"},{"key":"2020092513345167000_CIT0018","first-page":"445","article-title":"Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study","volume-title":"Exp Gerontol","author":"Wikby"},{"key":"2020092513345167000_CIT0019","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1016\/j.vaccine.2015.10.083","article-title":"Generation of switched memory B cells in response to vaccination in Down syndrome children and their siblings","volume":"33","author":"Valentini","year":"2015","journal-title":"Vaccine"},{"key":"2020092513345167000_CIT0020","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1365-2249.2011.04335.x","article-title":"Infections and immunodeficiency in Down syndrome","volume":"164","author":"Ram","year":"2011","journal-title":"Clin Exp Immunol"},{"key":"2020092513345167000_CIT0021","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/gerona\/glt120","article-title":"Evidence for less marked potential signs of T-cell immunosenescence in centenarian offspring than in the general age-matched population","volume":"69","author":"Pellican\u00f2","year":"2014","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2020092513345167000_CIT0022","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s40520-018-0936-7","article-title":"Sicilian centenarian offspring are more resistant to immune ageing","volume":"31","author":"Rubino","year":"2019","journal-title":"Aging Clin Exp Res"},{"key":"2020092513345167000_CIT0023","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mad.2015.03.006","article-title":"MARK-AGE biomarkers of ageing","volume":"151","author":"B\u00fcrkle","year":"2015","journal-title":"Mech Ageing Dev"},{"key":"2020092513345167000_CIT0024","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.mad.2015.03.007","article-title":"MARK-AGE standard operating procedures (SOPs): a successful effort","volume":"151","author":"Moreno-Villanueva","year":"2015","journal-title":"Mech Ageing Dev"},{"key":"2020092513345167000_CIT0025","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mad.2015.06.004","article-title":"Quality control data of physiological and immunological biomarkers measured in serum and plasma","volume":"151","author":"Jansen","year":"2015","journal-title":"Mech Ageing Dev"},{"key":"2020092513345167000_CIT0026","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.mad.2015.03.005","article-title":"The MARK-AGE phenotypic database: structure and strategy","volume":"151","author":"Moreno-Villanueva","year":"2015","journal-title":"Mech Ageing Dev"},{"key":"2020092513345167000_CIT0027","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.1128\/JCM.43.9.4807-4810.2005","article-title":"Relationships between total plasma load of torquetenovirus (TTV) and TTV genogroups carried","volume":"43","author":"Maggi","year":"2005","journal-title":"J Clin Microbiol"},{"key":"2020092513345167000_CIT0028","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s10522-017-9702-z","article-title":"The role of gender and labour status in immunosenescence of 65+ Polish population","volume":"18","author":"Dudkowska","year":"2017","journal-title":"Biogerontology"},{"key":"2020092513345167000_CIT0029","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s41232-018-0082-9","article-title":"The impact of senescence-associated T cells on immunosenescence and age-related disorders","volume":"38","author":"Fukushima","year":"2018","journal-title":"Inflamm Regen"},{"key":"2020092513345167000_CIT0030","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.exger.2014.01.010","article-title":"Chronic CMV infection in older women: longitudinal comparisons of CMV DNA in peripheral monocytes, anti-CMV IgG titers, serum IL-6 levels, and CMV pp65 (NLV)-specific CD8(+) T-cell frequencies with twelve year follow-up","volume":"54","author":"Li","year":"2014","journal-title":"Exp Gerontol"},{"key":"2020092513345167000_CIT0031","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s11357-012-9381-2","article-title":"The role of the T cell in age-related inflammation","volume":"35","author":"Macaulay","year":"2013","journal-title":"Age (Dordr)"},{"key":"2020092513345167000_CIT0032","first-page":"1155","article-title":"CD4:8 ratio above 5 is associated with all-cause mortality in CMV-seronegative very old women: results from the BELFRAIL study","volume":"72","author":"Adriaensen","year":"2017","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2020092513345167000_CIT0033","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3389\/fimmu.2013.00271","article-title":"Human T cell aging and the impact of persistent viral infections","volume":"4","author":"F\u00fcl\u00f6p","year":"2013","journal-title":"Front Immunol"},{"key":"2020092513345167000_CIT0034","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.leukres.2018.04.016","article-title":"High-dose zinc oral supplementation after stem cell transplantation causes an increase of TRECs and CD4+ na\u00efve lymphocytes and prevents TTV reactivation","volume":"70","author":"Iovino","year":"2018","journal-title":"Leuk Res"},{"key":"2020092513345167000_CIT0035","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.healun.2013.12.007","article-title":"Plasma DNA levels of Torque teno virus and immunosuppression after lung transplantation","volume":"33","author":"G\u00f6rzer","year":"2014","journal-title":"J Heart Lung Transplant"},{"key":"2020092513345167000_CIT0036","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/jmv.2052","article-title":"Prevalence and genotypic distribution of TT virus in Athens, Greece","volume":"65","author":"Katsoulidou","year":"2001","journal-title":"J Med Virol"},{"issue":"5","key":"2020092513345167000_CIT0037","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1203\/PDR.0b013e3181d4eca3","article-title":"Both normal memory counts and decreased naive cells favor intrinsic defect over early senescence of Down syndrome T lymphocytes","volume":"67","author":"Kusters","year":"2010","journal-title":"Pediatr Res"},{"key":"2020092513345167000_CIT0038","doi-asserted-by":"crossref","first-page":"e12903","DOI":"10.1111\/acel.12903","article-title":"Accelerated bio-cognitive aging in down syndrome: state of the art and possible deceleration strategies","volume":"18","author":"Franceschi","year":"2019","journal-title":"Aging Cell"},{"issue":"11","key":"2020092513345167000_CIT0039","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.micinf.2010.05.007","article-title":"Increased risk of respiratory tract infections in children with Down syndrome: the consequence of an altered immune system","volume":"12","author":"Bloemers","year":"2010","journal-title":"Microbes Infect"},{"key":"2020092513345167000_CIT0040","doi-asserted-by":"crossref","first-page":"248","DOI":"10.5114\/ceji.2018.80042","article-title":"Lymphocyte subgroups and recurrent infections in children with Down syndrome - a prospective case control study","volume":"43","author":"Mitwalli","year":"2018","journal-title":"Cent Eur J Immunol"},{"issue":"3","key":"2020092513345167000_CIT0041","doi-asserted-by":"crossref","first-page":"e20180225","DOI":"10.1542\/peds.2018-0225","article-title":"Down syndrome and the risk of severe RSV Infection: a meta-analysis","volume":"142","author":"Beckhaus","year":"2018","journal-title":"Pediatrics"},{"key":"2020092513345167000_CIT0042","first-page":"213","article-title":"Precocious aging of the immune system in Down syndrome: alteration of B lymphocytes, T-lymphocyte subsets, and cells with natural killer markers","volume":"7","author":"Cossarizza","year":"1990","journal-title":"Am J Med Genet Suppl"},{"key":"2020092513345167000_CIT0043","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1089\/rej.2007.0648","article-title":"Homeostatic cytokines and expansion of regulatory T cells accompany thymic impairment in children with Down syndrome","volume":"11","author":"Roat","year":"2008","journal-title":"Rejuvenation Res"},{"key":"2020092513345167000_CIT0044","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.exger.2014.01.023","article-title":"Immune parameters identify Italian centenarians with a longer five-year survival independent of their health and functional status","volume":"54","author":"Bucci","year":"2014","journal-title":"Exp Gerontol"},{"key":"2020092513345167000_CIT0045","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1093\/infdis\/jix168","article-title":"Quantitative, phenotypical, and functional characterization of cellular immunity in children and adolescents with down syndrome","volume":"215","author":"Schoch","year":"2017","journal-title":"J Infect Dis"},{"key":"2020092513345167000_CIT0046","doi-asserted-by":"crossref","first-page":"15490","DOI":"10.1038\/s41598-018-33909-7","article-title":"Early post-transplant torquetenovirus viremia predicts cytomegalovirus reactivations in solid organ transplant recipients","volume":"8","author":"Maggi","year":"2018","journal-title":"Sci Rep"},{"key":"2020092513345167000_CIT0047","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/jmv.10129","article-title":"High TT virus load as an independent factor associated with the occurrence of hepatocellular carcinoma among patients with hepatitis C virus-related chronic liver disease","volume":"67","author":"Tokita","year":"2002","journal-title":"J Med Virol"},{"key":"2020092513345167000_CIT0048","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s10096-016-2851-1","article-title":"The impact of chronic hepatitis C infection on cholesterol metabolism in PBMCs is associated with microRNA-146a expression","volume":"36","author":"Sidorkiewicz","year":"2017","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2020092513345167000_CIT0049","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s10522-009-9251-1","article-title":"Plasma copper\/zinc ratio: an inflammatory\/nutritional biomarker as predictor of all-cause mortality in elderly population","volume":"11","author":"Malavolta","year":"2010","journal-title":"Biogerontology"},{"key":"2020092513345167000_CIT0050","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1007\/s00394-016-1281-2","article-title":"Main biomarkers associated with age-related plasma zinc decrease and copper\/zinc ratio in healthy elderly from ZincAge study","volume":"56","author":"Giacconi","year":"2017","journal-title":"Eur J Nutr"},{"issue":"Pt 2","key":"2020092513345167000_CIT0051","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1258\/000456303763046067","article-title":"Immunoglobulins and immunoglobulin subclasses in the elderly","volume":"40","author":"Lock","year":"2003","journal-title":"Ann Clin Biochem"},{"key":"2020092513345167000_CIT0052","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1002\/eji.201445049","article-title":"Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome","volume":"45","author":"Carsetti","year":"2015","journal-title":"Eur J Immunol"},{"key":"2020092513345167000_CIT0053","doi-asserted-by":"crossref","first-page":"604","DOI":"10.2174\/138161210790883750","article-title":"B cells compartment in centenarian offspring and old people","volume":"16","author":"Colonna-Romano","year":"2010","journal-title":"Curr Pharm Des"}],"container-title":["The Journals of Gerontology: Series A"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/biomedgerontology\/advance-article-pdf\/doi\/10.1093\/gerona\/glz293\/31835559\/glz293.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/75\/10\/1838\/33792839\/glz293.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/75\/10\/1838\/33792839\/glz293.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T13:35:47Z","timestamp":1601040947000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article\/75\/10\/1838\/5678083"}},"subtitle":[],"editor":[{"given":"David","family":"Le Couteur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,12,15]]},"references-count":53,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,12,15]]},"published-print":{"date-parts":[[2020,9,25]]}},"URL":"https:\/\/doi.org\/10.1093\/gerona\/glz293","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737092077.793569979","asserted-by":"object"}]},"ISSN":["1079-5006","1758-535X"],"issn-type":[{"value":"1079-5006","type":"print"},{"value":"1758-535X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,10]]},"published":{"date-parts":[[2019,12,15]]}}}