Corneal Endothelial Cells Provide Evidence of Accelerated Cellular Senescence Associated with HIV Infection: A Case-Control Study

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Abstract

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.<br /><br />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.<br /><br />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.<br /><br />CONCLUSIONS: The corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery.

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Pathai, S., Lawn, S. D., Shiels, P. G., Weiss, H. A., Cook, C., Wood, R., & 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). https://doi.org/10.1371/journal.pone.0057422

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