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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7830696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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