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The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging

According to the WHO, 38 million individuals were living with human immunodeficiency virus (HIV), 25.4 million of which were using antiretroviral therapy (ART) at the end of 2019. Despite ART-mediated suppression of viral replication, ART is not a cure and is associated with viral persistence, resid...

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Autores principales: Schank, Madison, Zhao, Juan, Moorman, Jonathan P., Yao, Zhi Q.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830696/
https://www.ncbi.nlm.nih.gov/pubmed/33467074
http://dx.doi.org/10.3390/cells10010174
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author Schank, Madison
Zhao, Juan
Moorman, Jonathan P.
Yao, Zhi Q.
author_facet Schank, Madison
Zhao, Juan
Moorman, Jonathan P.
Yao, Zhi Q.
author_sort Schank, Madison
collection PubMed
description According to the WHO, 38 million individuals were living with human immunodeficiency virus (HIV), 25.4 million of which were using antiretroviral therapy (ART) at the end of 2019. Despite ART-mediated suppression of viral replication, ART is not a cure and is associated with viral persistence, residual inflammation, and metabolic disturbances. Indeed, due to the presence of viral reservoirs, lifelong ART therapy is required to control viremia and prevent disease progression into acquired immune deficiency syndrome (AIDS). Successful ART treatment allows people living with HIV (PLHIV) to achieve a similar life expectancy to uninfected individuals. However, recent studies have illustrated the presence of increased comorbidities, such as accelerated, premature immune aging, in ART-controlled PLHIV compared to uninfected individuals. Studies suggest that both HIV-infection and ART-treatment lead to mitochondrial dysfunction, ultimately resulting in cellular exhaustion, senescence, and apoptosis. Since mitochondria are essential cellular organelles for energy homeostasis and cellular metabolism, their compromise leads to decreased oxidative phosphorylation (OXPHOS), ATP synthesis, gluconeogenesis, and beta-oxidation, abnormal cell homeostasis, increased oxidative stress, depolarization of the mitochondrial membrane potential, and upregulation of mitochondrial DNA mutations and cellular apoptosis. The progressive mitochondrial damage induced by HIV-infection and ART-treatment likely contributes to accelerated aging, senescence, and cellular dysfunction in PLHIV. This review discusses the connections between mitochondrial compromise and cellular dysfunction associated with HIV- and ART-induced toxicities, providing new insights into how HIV and current ART directly impact mitochondrial functions and contribute to cellular senescence and aging in PLHIV. Identifying this nexus and potential mechanisms may be beneficial in developing improved therapeutics for treating PLHIV.
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spelling pubmed-78306962021-01-26 The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging Schank, Madison Zhao, Juan Moorman, Jonathan P. Yao, Zhi Q. Cells Review According to the WHO, 38 million individuals were living with human immunodeficiency virus (HIV), 25.4 million of which were using antiretroviral therapy (ART) at the end of 2019. Despite ART-mediated suppression of viral replication, ART is not a cure and is associated with viral persistence, residual inflammation, and metabolic disturbances. Indeed, due to the presence of viral reservoirs, lifelong ART therapy is required to control viremia and prevent disease progression into acquired immune deficiency syndrome (AIDS). Successful ART treatment allows people living with HIV (PLHIV) to achieve a similar life expectancy to uninfected individuals. However, recent studies have illustrated the presence of increased comorbidities, such as accelerated, premature immune aging, in ART-controlled PLHIV compared to uninfected individuals. Studies suggest that both HIV-infection and ART-treatment lead to mitochondrial dysfunction, ultimately resulting in cellular exhaustion, senescence, and apoptosis. Since mitochondria are essential cellular organelles for energy homeostasis and cellular metabolism, their compromise leads to decreased oxidative phosphorylation (OXPHOS), ATP synthesis, gluconeogenesis, and beta-oxidation, abnormal cell homeostasis, increased oxidative stress, depolarization of the mitochondrial membrane potential, and upregulation of mitochondrial DNA mutations and cellular apoptosis. The progressive mitochondrial damage induced by HIV-infection and ART-treatment likely contributes to accelerated aging, senescence, and cellular dysfunction in PLHIV. This review discusses the connections between mitochondrial compromise and cellular dysfunction associated with HIV- and ART-induced toxicities, providing new insights into how HIV and current ART directly impact mitochondrial functions and contribute to cellular senescence and aging in PLHIV. Identifying this nexus and potential mechanisms may be beneficial in developing improved therapeutics for treating PLHIV. MDPI 2021-01-16 /pmc/articles/PMC7830696/ /pubmed/33467074 http://dx.doi.org/10.3390/cells10010174 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Schank, Madison
Zhao, Juan
Moorman, Jonathan P.
Yao, Zhi Q.
The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging
title The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging
title_full The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging
title_fullStr The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging
title_full_unstemmed The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging
title_short The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging
title_sort impact of hiv- and art-induced mitochondrial dysfunction in cellular senescence and aging
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830696/
https://www.ncbi.nlm.nih.gov/pubmed/33467074
http://dx.doi.org/10.3390/cells10010174
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