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

Abstract

BackgroundCellular 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.MethodsCase-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.ResultsThe 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.ConclusionsThe corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery.

Corneal Confocal Microscopy detects a Reduction in Corneal Endothelial Cells and Nerve Fibres in Patients with Acute Ischemic Stroke

“…In a study of children with Type 1 diabetes, polymegathism was increased, but pleomorphism was reduced 25 . In subjects with HIV, endothelial cell density was preserved, but polymegathism was increased 45 . In the present study we also show no difference in endothelial cell morphology between patients with and without diabetes, but an association with triglycerides diastolic blood pressure and HDL.…”

Ageing and ocular surface immunity

“…45 For example, corneal endothelial cells in patients with HIV show increased variation in cell size and lower cell density, consistent with HIV-related accelerated senescence, especially among those with poor immune recovery. 46 The effect of HIV on other cell types and resident immune cells is poorly understood and remains to be investigated; however, it is known that both HIV infection and ageing are characterised by a deficiency in the number of competent T cells. Recent studies show that antiretroviral therapy, despite the adequate recovery of CD4+ T cell counts and suppression of viremia, is less efficient in restoring the immune system in older patients.…”

Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label Clinical Trial

“…Increased oxidative genomic (DNA) damage has been reported in younger PWH < 60 years [ 45 ], and has been linked to accelerated aging [ 17 , 46 ] and cognitive impairment [ 47 ]. Mechanisms contributing to genomic damage are unclear, and interventions lacking.…”

“…Other reports have linked early aging in PWH to diverse health conditions ranging from declining gait speed [ 8 ], physical function [ 9 ] and cognition [ 10 , 11 ], mitochondrial aging [ 12 , 13 ], and elevated inflammation [ 14 , 15 , 16 ]. Additional evidence for early aging in PWH comes from studies in corneal epithelial cells, monocyte, and immune dysfunction, and the emergence of frailty at an earlier age [ 6 , 7 , 17 ]. Although premature aging in PWH is now being recognized as a new, significant public health challenge, there is limited knowledge about underlying causal mechanisms, and effective interventions are lacking.…”