Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study

Pathai, S., Lawn, S.D., Shiels, P.G. , Weiss, H.A., Cook, C., Wood, R. and Gilbert, C.E. (2013) Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study. PLoS ONE, 8(2), e57422. (doi: 10.1371/journal.pone.0057422) (PMID:23460854) (PMCID:PMC3584030)

Abstract

<p>Background: Cellular senescence may be a key factor in HIV-related premature biological aging. We assessed features of the corneal endothelium that are known to be associated with biological aging, and cellular senescence markers in HIV-infected adults.</p> <p>Methods: Case-control study of 242 HIV-infected adults and 249 matched controls. Using specular microscopy, the corneal endothelium was assessed for features of aging (low endothelial cell density [ECD], high variation in cell size, and low hexagonality index). Data were analysed by multivariable regression. CDKN2A expression (a cell senescence mediator) was measured in peripheral blood leukocytes and 8-hydroxy-2′-deoxyguanosine (8-OHDG; an oxidative DNA damage marker) levels were measured in plasma.</p> <p>Results: The median age of both groups was 40 years. Among HIV-infected adults, 88% were receiving antiretroviral therapy (ART); their median CD4 count was 468 cells/µL. HIV infection was associated with increased odds of variation in cell size (OR = 1.67; 95% CI: 1.00–2.78, p = 0.04). Among HIV-infected participants, low ECD was independently associated with current CD4 count <200 cells/µL (OR = 2.77; 95%CI: 1.12–6.81, p = 0.03). In participants on ART with undetectable viral load, CDKN2A expression and 8-OHDG levels were higher in those with accelerated aging, as reflected by lower ECD.</p> <p>Conclusions: The corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery.</p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Shiels, Professor Paul
• Authors: Pathai, S., Lawn, S.D., Shiels, P.G., Weiss, H.A., Cook, C., Wood, R., and Gilbert, C.E.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• Published Online: 27 February 2013
• Copyright Holders: Copyright © 2013 The Authors
• First Published: First published in PLoS ONE 8(2):e57422
• Publisher Policy: Reproduced under a Creative Commons License