ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2021
Mitochondrial DNA Damage and Brain Aging in Human Immunodeficiency Virus.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Comprehensive summary of mitochondrial DNA alterations in the postmortem human brain: A systematic review.EBioMedicine · 2022Pooled it
- Alterations of Brain Metabolites in Adults With HIV: A Systematic Meta-analysis of Magnetic Resonance Spectroscopy Studies.Neurology · 2021Pooled it
- Lipid metabolism and neurodegeneration: Mechanistic insights and therapeutic targets.Ageing research reviews · 2026Review
- HIV Infection, Neurotoxicity, Inflammation, Premature Aging, and Therapeutic Challenges to PLWH: An Overview.International journal of molecular sciences · 2026Review
- Mitochondria in SARS-CoV-2 infection: Immune interactions and molecular approaches in the Post COVID-19 condition.Genetics and molecular biology · 2026Article
- The Role of Nutrition in HIV-Associated Neurocognitive Disorders: Mechanisms, Risks, and Interventions.Life (Basel, Switzerland) · 2025Review
- Impact of low-level viremia on HIV non-viral load suppression in low and middle-income countries.Annals of medicine and surgery (2012) · 2025Review
- Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances.Signal transduction and targeted therapy · 2025Review
- Mitochondrial DNA damage in HIV infection: a mechanistic driver of immunometabolic dysfunction and chronic inflammation.Frontiers in immunology · 2025Review
- Ventricular volume adjustment of brain regions depicts brain changes associated with HIV infection and aging better than intracranial volume adjustment.Frontiers in neurology · 2025Article
- Intestinal Microbiota and Aging in People with HIV-What We Know and What We Don't.Current HIV/AIDS reports · 2024Review
- The Impact of HIV on Early Brain Aging-A Pathophysiological (Re)View.Journal of clinical medicine · 2024Review
- Mitochondrial DNA and Electron Transport Chain Protein Levels Are Altered in Peripheral Nerve Tissues from Donors with HIV Sensory Neuropathy: A Pilot Study.International journal of molecular sciences · 2024Article
- Mitochondrial variants of complex I genes associated with leprosy clinical subtypes.Scientific reports · 2024Article
- Whole mitogenome sequencing uncovers a relation between mitochondrial heteroplasmy and leprosy severity.Human genomics · 2023Article
- Mitoquinone Mesylate and Mitochondrial DNA in End Organs in Humanized Mouse Model of Chronic Treated Human Immunodeficiency Virus Infection.The Journal of infectious diseases · 2023Article
- Review
- HIV-Proteins-Associated CNS Neurotoxicity, Their Mediators, and Alternative Treatments.Cellular and molecular neurobiology · 2022Review
- Long-Term Persistence of Mitochondrial DNA Instability in HIV-Exposed Uninfected Children during and after Exposure to Antiretroviral Drugs and HIV.Biomedicines · 2022Article
- Small Vessel Disease: Ancient Description, Novel Biomarkers.International journal of molecular sciences · 2022Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundNeurocognitive impairment (NCI) remains common in people living with human immunodeficiency virus (PLWH), despite suppressive antiretroviral therapy (ART), but the reasons remain incompletely understood. Mitochondrial dysfunction is a hallmark of aging and of neurodegenerative diseases. We hypothesized that human immunodeficiency virus (HIV) or ART may lead to mitochondrial abnormalities in the brain, thus contributing to NCI.
methodsWe studied postmortem frozen brain samples from 52 PLWH and 40 HIV-negative controls. Cellular mitochondrial DNA (mtDNA) content and levels of large-scale mtDNA deletions were measured by real-time polymerase chain reaction. Heteroplasmic mtDNA point mutations were quantified by deep sequencing (Illumina). Neurocognitive data were taken within 48 months antemortem.
resultsWe observed a decrease in mtDNA content, an increase in the mtDNA "common deletion," and an increase in mtDNA point mutations with age (all P < .05). Each of these changes was exacerbated in HIV-positive cases compared with HIV-negative controls (all P < .05). ART exposures, including nucleoside analogue reverse transcriptase inhibitors, were not associated with changes in mtDNA. The number of mtDNA point mutations was associated with low CD4/CD8 ratio (P = .04) and with NCI (global T-score, P = .007).
conclusionsIn people with predominantly advanced HIV infection, there is exacerbation of age-associated mtDNA damage. This change is driven by HIV per se rather than by ART toxicity and may contribute to NCI. These data suggest that mitochondrial dysfunction may be a mediator of adverse aging phenotypes in PLWH.
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