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

PLoS One. 2013;8(2):e57422. doi: 10.1371/journal.pone.0057422. Epub 2013 Feb 27.

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.

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.

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.

Conclusions: The corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cell Count
  • Cell Shape
  • Cell Size
  • Cellular Senescence*
  • Endothelial Cells / pathology*
  • Endothelium, Corneal / pathology*
  • Female
  • HIV Infections / pathology*
  • Humans
  • Male
  • Middle Aged
  • Models, Biological
  • Multivariate Analysis

Substances

  • Biomarkers