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HIV antiretroviral therapy drugs induce premature senescence and altered physiology in HUVECs
Journal article   Open access   Peer reviewed

HIV antiretroviral therapy drugs induce premature senescence and altered physiology in HUVECs

Justin Cohen, Luca D'Agostino, Ferit Tuzer and Claudio Torres
Mechanisms of ageing and development, v 175, pp 74-82
Oct 2018
DOI: https://doi.org/10.1016/j.mad.2018.07.008
PMID: 30055190
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.3722/cadaps.2008.363-370View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Anti-HIV Agents - toxicity Astrocytes - drug effects Astrocytes - metabolism Astrocytes - pathology Cell Proliferation - drug effects Cells, Cultured Cellular Senescence - drug effects Emtricitabine - toxicity Human Umbilical Vein Endothelial Cells - drug effects Human Umbilical Vein Endothelial Cells - metabolism Human Umbilical Vein Endothelial Cells - pathology Humans Inflammation Mediators - metabolism Nitric Oxide Synthase Type III - metabolism Oxidative Stress - drug effects Paracrine Communication - drug effects Tenofovir - toxicity
Developments in medicine have led to a significant increase in the average human lifespan. This increase in aging is most readily apparent in the case of HIV where antiretroviral therapy has shifted infection from a terminal to a chronic but manageable disease. Despite this advance, patients suffer from co-morbidities best described as an accelerated aging phenotype. A potential contributor is cellular senescence, an aging-associated growth arrest, which has already been linked to other HIV co-morbidities such as lipodystrophies and osteoporosis in response to antiretroviral drugs. We have previously demonstrated that astrocytes senescence in response to antiretroviral drugs. As endothelial cells play a critical role regulating the blood brain barrier (BBB) and senescence could severely impact barrier permeability, we investigate the role of a commonly used combination of HIV reverse transcriptase inhibitors on the senescence program of human umbilical vein endothelial cells (HUVECs). Our studies indicate that HUVECs underwent premature senescence associated with inflammation, oxidative stress and altered eNOS activation. Treated cells had detrimental paracrine effects on astrocytes including paracrine senescence, suggesting that senescent HUVECs could influence astrocytes, which line the other side of the BBB. These results may have implications for HIV-associated neurocognitive disorders (HAND), a set of neurological deficits.

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25 citations in Web of Science
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Web of Science research areas
Cell Biology
Geriatrics & Gerontology
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