title: Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study.
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.
authors: International Centre for Eye Health, Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom. Sophia.pathai@lshtm.ac.uk
authors: Sophia
authors: S
authors: Pathai
authors: Stephen D
authors: SD
authors: Lawn
authors: Paul G
authors: PG
authors: Shiels
authors: Helen A
authors: HA
authors: Weiss
authors: Colin
authors: C
authors: Cook
authors: Robin
authors: R
authors: Wood
authors: Clare E
authors: CE
authors: Gilbert
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002452:Cell Count; D048430:Cell Shape; D048429:Cell Size; D016922:Cellular Senescence; D042783:Endothelial Cells / Q000473:pathology*; D004728:Endothelium, Corneal / Q000473:pathology*; D005260:Female; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis
chemical_list: D015415:Biomarkers