{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T22:24:25Z","timestamp":1778019865758,"version":"3.51.4"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2013,2,27]],"date-time":"2013-02-27T00:00:00Z","timestamp":1361923200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0057422","type":"journal-article","created":{"date-parts":[[2013,2,27]],"date-time":"2013-02-27T22:49:30Z","timestamp":1362005370000},"page":"e57422","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Corneal Endothelial Cells Provide Evidence of Accelerated Cellular Senescence Associated with HIV Infection: A Case-Control Study"],"prefix":"10.1371","volume":"8","author":[{"given":"Sophia","family":"Pathai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen D.","family":"Lawn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul G.","family":"Shiels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen A.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Cook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Wood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clare E.","family":"Gilbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2013,2,27]]},"reference":[{"key":"ref1","first-page":"118","article-title":"Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy","volume":"17","author":"SG Deeks","year":"2009","journal-title":"Top HIV Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.7326\/0003-4819-146-2-200701160-00003","article-title":"Survival of persons with and without HIV infection in Denmark, 1995\u20132005","volume":"146","author":"N Lohse","year":"2007","journal-title":"Ann Intern Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1167\/iovs.08-3007","article-title":"Relationship among oxidative stress, DNA damage, and proliferative capacity in human corneal endothelium","volume":"50","author":"NC Joyce","year":"2009","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.gde.2010.10.005","article-title":"Cellular senescence: putting the paradoxes in perspective","volume":"21","author":"J Campisi","year":"2011","journal-title":"Current Opinion in Genetics & Development"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.exer.2011.08.014","article-title":"Proliferative capacity of corneal endothelial cells","volume":"95","author":"NC Joyce","year":"2012","journal-title":"Experimental Eye Research"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.exer.2003.08.002","article-title":"Clinical responses of the corneal endothelium","volume":"78","author":"WM Bourne","year":"2004","journal-title":"Experimental Eye Research"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/S0002-9394(02)02237-7","article-title":"Increased endothelial cell density in the paracentral and peripheral regions of the human cornea","volume":"135","author":"J Amann","year":"2003","journal-title":"Am J Ophthalmol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/0014-4835(76)90003-8","article-title":"Changes in the corneal endothelium as a function of age","volume":"22","author":"RA Laing","year":"1976","journal-title":"Exp Eye Res"},{"key":"ref9","first-page":"423","article-title":"Corneal endothelial cell density decreases with age in emmetropic eyes","volume":"20","author":"JA Sanchis-Gimeno","year":"2005","journal-title":"Histol Histopathol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1136\/bjo.66.8.513","article-title":"Effect of age on the endothelial cell count in the normal eye","volume":"66","author":"RS Wilson","year":"1982","journal-title":"Br J Ophthalmol"},{"key":"ref11","first-page":"779","article-title":"Central corneal endothelial cell changes over a ten-year period","volume":"38","author":"WM Bourne","year":"1997","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"671","DOI":"10.3109\/02713688509017661","article-title":"Changes in the normal corneal endothelial cellular pattern as a function of age","volume":"4","author":"RW Yee","year":"1985","journal-title":"Curr Eye Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1001\/archopht.1985.01050100054017","article-title":"Precision of cell density estimates and endothelial cell loss with age","volume":"103","author":"H Cheng","year":"1985","journal-title":"Arch Ophthalmol"},{"key":"ref14","first-page":"803","article-title":"High expression of p16INK4a and low expression of Bmi1 are associated with endothelial cellular senescence in the human cornea","volume":"18","author":"Y Wang","year":"2012","journal-title":"Mol Vis"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1167\/iovs.03-0814","article-title":"Proliferative Response of Corneal Endothelial Cells from Young and Older Donors","volume":"45","author":"C Zhu","year":"2004","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1474-9726.2008.00447.x","article-title":"Cellular senescence in pretransplant renal biopsies predicts postoperative organ function","volume":"8","author":"LM McGlynn","year":"2009","journal-title":"Aging Cell"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/j.1474-9726.2008.00398.x","article-title":"Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation","volume":"7","author":"C Koppelstaetter","year":"2008","journal-title":"Aging Cell"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"16562","DOI":"10.1073\/pnas.0904405106","article-title":"A quantitative model for age-dependent expression of the p16INK4a tumor suppressor","volume":"106","author":"D Tsygankov","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1474-9726.2009.00489.x","article-title":"Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging","volume":"8","author":"Y Liu","year":"2009","journal-title":"Aging Cell"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/j.1365-2796.2007.01890.x","article-title":"Telomere attrition is associated with inflammation, low fetuin-A levels and high mortality in prevalent haemodialysis patients","volume":"263","author":"JJ Carrero","year":"2008","journal-title":"J Intern Med"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1097\/QAD.0b013e3283493fb0","article-title":"Risk of cerebrovascular events in persons with and without HIV: a Danish nationwide population-based cohort study","volume":"25","author":"LD Rasmussen","year":"2011","journal-title":"AIDS"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1093\/cid\/cir627","article-title":"Premature Age-Related Comorbidities Among HIV-Infected Persons Compared With the General Population","volume":"53","author":"G Guaraldi","year":"2011","journal-title":"Clinical Infectious Diseases"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1097\/QAD.0b013e3283174636","article-title":"The role of HIV in serious diseases other than AIDS","volume":"22","author":"AN Phillips","year":"2008","journal-title":"AIDS"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/cid\/cir628","article-title":"Premature Aging and Premature Age-Related Comorbidities in HIV-Infected Patients: Facts and Hypotheses","volume":"53","author":"J Capeau","year":"2011","journal-title":"CLIN INFECT DIS"},{"key":"ref25","first-page":"43","article-title":"Frailty in HIV-infected adults in South Africa. J Acquir Immune Defic Syndr","volume":"62","author":"S Pathai","year":"2012"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e51405","DOI":"10.1371\/journal.pone.0051405","article-title":"Retinal arterioles narrow with increasing duration of anti-retroviral therapy in HIV infection: a novel estimator of vascular risk in HIV","volume":"7","author":"S Pathai","year":"2012","journal-title":"PLoS ONE"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1097\/01.aids.0000238406.93249.cd","article-title":"Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control","volume":"20","author":"SD Lawn","year":"2006","journal-title":"AIDS"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1097\/01.aids.0000194802.89540.e1","article-title":"Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design","volume":"19","author":"SD Lawn","year":"2005","journal-title":"AIDS"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1474-9726.2011.00776.x","article-title":"Characterization of cellular senescence mechanisms in human corneal endothelial cells","volume":"11","author":"AN Sheerin","year":"2012","journal-title":"Aging Cell"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1016\/j.freeradbiomed.2011.09.025","article-title":"Corneal damage and lacrimal gland dysfunction in a smoking rat model","volume":"51","author":"A Higuchi","year":"2011","journal-title":"Free Radical Biology and Medicine"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/ICO.0b013e31815892da","article-title":"Review of corneal endothelial specular microscopy for FDA clinical trials of refractive procedures, surgical devices, and new intraocular drugs and solutions","volume":"27","author":"BE Mccarey","year":"2008","journal-title":"Cornea"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/0002-9394(84)90120-X","article-title":"Corneal endothelial changes in type I and type II diabetes mellitus","volume":"98","author":"RO Schultz","year":"1984","journal-title":"Am J Ophthalmol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/00003226-199203000-00007","article-title":"Histopathological analysis of corneal endothelial polymegethism","volume":"11","author":"JP Bergmanson","year":"1992","journal-title":"Cornea"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrm2233","article-title":"Cellular senescence: when bad things happen to good cells","volume":"8","author":"J Campisi","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev-med-042909-093756","article-title":"HIV infection, inflammation, immunosenescence, and aging","volume":"62","author":"SG Deeks","year":"2011","journal-title":"Annu Rev Med"},{"key":"ref37","first-page":"161","article-title":"Expression of senescence-related genes in human corneal endothelial cells","volume":"14","author":"Z Song","year":"2008","journal-title":"Mol Vis"},{"key":"ref38","first-page":"747","article-title":"Molecular evidence of senescence in corneal endothelial cells of senescence-accelerated mice","volume":"15","author":"X Xiao","year":"2009","journal-title":"Mol Vis"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/1097-0215(20010601)92:5<622::AID-IJC1256>3.0.CO;2-K","article-title":"A case-control study of human immunodeficiency virus infection and cancer in adults and children residing in Kampala, Uganda","volume":"92","author":"R Newton","year":"2001","journal-title":"Int J Cancer"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Waddell K, Kwehangana J, Johnston WT, Lucas S, Newton R (2010) A case-control study of ocular surface squamous neoplasia (OSSN) in Uganda. Int J Cancer 127 427\u2013432.","DOI":"10.1002\/ijc.25040"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/QCO.0b013e32834f14fa","article-title":"HIV and ageing: premature ageing or premature conclusions","volume":"25","author":"M Fisher","year":"2012","journal-title":"Curr Opin Infect Dis"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"477","DOI":"10.7326\/0003-4819-153-7-201010050-00013","article-title":"HIV and premature aging: A field still in its infancy","volume":"153","author":"J Martin","year":"2010","journal-title":"Ann Intern Med"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S0002-9394(99)00086-0","article-title":"Corneal endothelial changes in patients with chronic renal failure","volume":"128","author":"N Ohguro","year":"1999","journal-title":"Am J Ophthalmol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1001\/archopht.1996.01100130007001","article-title":"Structure and function of the corneal endothelium in diabetes mellitus type I and type II","volume":"114","author":"LI Larsson","year":"1996","journal-title":"Arch Ophthalmol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/sj.eye.6701868","article-title":"Differences in corneal thickness and corneal endothelium related to duration in diabetes","volume":"20","author":"JS Lee","year":"2006","journal-title":"Eye (Lond)"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/QAD.0b013e328340fe91","article-title":"Intraocular and plasma HIV-1 RNA loads and HIV uveitis","volume":"25","author":"K Pathanapitoon","year":"2011","journal-title":"AIDS (London, England)"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1097\/COH.0b013e328302cc3d","article-title":"Ocular immune reconstitution inflammatory syndromes","volume":"3","author":"J Otiti-Sengeri","year":"2008","journal-title":"Curr Opin HIV AIDS"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/j.1365-3156.2010.02712.x","article-title":"Differing spectrum of HIV-associated ophthalmic disease among patients starting antiretroviral therapy in India and South Africa","volume":"16","author":"S Pathai","year":"2011","journal-title":"Trop Med Int Health"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"a3172","DOI":"10.1136\/bmj.a3172","article-title":"HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity","volume":"338","author":"SG Deeks","year":"2009","journal-title":"BMJ"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0057422","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T21:41:26Z","timestamp":1540244486000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0057422"}},"subtitle":[],"editor":[{"given":"Yingfeng","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2013,2,27]]},"references-count":49,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2013,2,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0057422","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,27]]}}}