Biological Aging in People Living with HIV on Successful Antiretroviral Therapy: Do They Age Faster?

Akusjärvi, Sara Svensson; Neogi, Ujjwal

doi:10.1007/s11904-023-00646-0

Cited by 10 publications

(12 citation statements)

References 85 publications

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“…As PWH presents a complex aging process and is confounded by the ART, sex, genetics, environment, lifestyle, and comorbidities (Akusjarvi & Neogi, 2023), recent studies reported epigenetic age acceleration in PWH (Breen et al, 2022;Esteban-Cantos et al, 2021) limited by those confounders observed in our study.…”

contrasting

confidence: 45%

Transcriptomics age acceleration in prolonged treated HIV infection

Mikaeloff,

Gelpi,

Escos

et al. 2023

Aging Cell

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Biological aging in people with HIV (PWH) with prolonged successful antiretroviral therapy (ART) is convoluted and poorly defined. Here, we aimed to investigate the transcriptomics age estimator (TAE) in a cohort of 178 PWH on prolonged successful ART with immune reconstitution and viral suppression from the Copenhagen Comorbidity (COCOMO) cohort. We also used 143 clinical, demographical, and lifestyle factors to identify the confounders potentially responsible or associated with age acceleration. Among the PWH, 43% had an accelerated aging process (AAP), and 21% had decelerated aging process (DAP). DAP is linked with older age, European ancestry, and higher use of tenofovir disoproxil/alafenamide fumarate. A directionally class‐based gene set enrichment analysis identified the upregulation of inflammatory pathways (e.g., cytokine and Retinoic acid‐inducible gene I (RIG‐I)‐like receptor signaling pathways) and immune response like T‐cell receptor signaling, antigen processing, and presentation in AAP and the downregulation of metabolic processes like oxidative phosphorylation, pyruvate metabolism.

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contrasting

confidence: 45%

Transcriptomics age acceleration in prolonged treated HIV infection

Mikaeloff,

Gelpi,

Escos

et al. 2023

Aging Cell

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“…Additionally, our results showed that those who were diagnosed with HIV at an older age exhibited increased epigenetic aging. Prior to DNAm-based measures of epigenetic aging, several studies have reported increased incidence of age-related phenotypes and biological changes associated with aging in PLHIV, which occurred at a significantly younger age compared to non-infected counterparts [ 17 , 56 , 57 ]. This has been further established with the recent improvement in epigenetic clocks, with results showing that epigenetic and biological age is accelerated in PLHIV compared to HIV-uninfected individuals, although most of these studies were conducted in higher-income countries [ 38 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic aging in older people living with HIV in Eswatini: a pilot study of HIV and lifestyle factors and epigenetic aging

Dye,

Wu,

Jackson

et al. 2024

Clin Epigenet

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Background People living with HIV (PLHIV) on effective antiretroviral therapy are living near-normal lives. Although they are less susceptible to AIDS-related complications, they remain highly vulnerable to non-communicable diseases. In this exploratory study of older PLHIV (OPLHIV) in Eswatini, we investigated whether epigenetic aging (i.e., the residual between regressing epigenetic age on chronological age) was associated with HIV-related parameters, and whether lifestyle factors modified these relationships. We calculated epigenetic aging focusing on the Horvath, Hannum, PhenoAge and GrimAge epigenetic clocks, and a pace of biological aging biomarker (DunedinPACE) among 44 OPLHIV in Eswatini. Results Age at HIV diagnosis was associated with Hannum epigenetic age acceleration (EAA) (β-coefficient [95% Confidence Interval]; 0.53 [0.05, 1.00], p = 0.03) and longer duration since HIV diagnosis was associated with slower Hannum EAA (− 0.53 [− 1.00, − 0.05], p = 0.03). The average daily dietary intake of fruits and vegetables was associated with DunedinPACE (0.12 [0.03, 0.22], p = 0.01). The associations of Hannum EAA with the age at HIV diagnosis and duration of time since HIV diagnosis were attenuated when the average daily intake of fruits and vegetables or physical activity were included in our models. Diet and self-perceived quality of life measures modified the relationship between CD4+ T cell counts at participant enrollment and Hannum EAA. Conclusions Epigenetic age is more advanced in OPLHIV in Eswatini in those diagnosed with HIV at an older age and slowed in those who have lived for a longer time with diagnosed HIV. Lifestyle and quality of life factors may differentially affect epigenetic aging in OPLHIV. To our knowledge, this is the first study to assess epigenetic aging in OPLHIV in Eswatini and one of the few in sub-Saharan Africa.

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“…Taylor et al, demonstrated that increased glycolysis, through the modulation of mTOR, can facilitate HIV-1 permissiveness through increasing dNTP pools required for early steps of HIV-1 replication as well as acetyl-CoA required for nuclear transportation of viral products 127 . Ono et al ., have demonstrated that increased lipid synthesis, through the modulation of mTOR, can complete the viral life cycle by increasing the level of cholesterol and membrane lipids required for the late steps of HIV-1 budding 136 . Besnard et al demonstrated that both mTORC1 and mTORC2 are essential for HIV-1 reactivation from latency 137 and suggested that mTOR inhibition activates the autophagy pathway, which has been demonstrated to repress HIV production through Tat degradation in CD4 + T cells 138 .…”

Section: Discussionmentioning

confidence: 99%

Retinoic Acid Boosts HIV-1 Replication in MacrophagesviaCCR5/SAMHD1-Dependent and mTOR-Modulated Mechanisms

Dias,

Cattin,

Goulet

et al. 2023

Preprint

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The intestinal environment facilitates HIV-1 infectionviamechanisms involving the gut-homing elixir retinoic acid (RA), which transcriptionally reprograms CD4+T-cells for increased HIV-1 permissiveness. Consistently, colon-infiltrating CD4+T-cells carry replication-competent viral reservoirs in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Intriguingly, integrative infection in colon macrophages, a pool replenished by circulating monocytes, represents a rare event in ART-treated PLWH, thus questioning on HIV-1 permissiveness in gut-resident macrophages. Here, we demonstrate that RA significantly boosts R5 but not X4 HIV-1 replication in monocyte-derived macrophages (MDMs). RNA-Sequencing, Gene Set Variation Analysis, and HIV interactor NCBI database interrogation, revealed RA- mediated transcriptional reprogramming associated with metabolic/inflammatory processes and HIV-1 resistance/dependency factors. Functional validations pointed to mechanisms of RA action, including CCR5 upregulation and SAMHD1 phosphorylation under the control of mTOR. These results support a model in which intestinal MDM contribute to viral replication/dissemination before ART and upon treatment interruption in mTOR-sensitive manner.Figure 1:

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Biological Aging in People Living with HIV on Successful Antiretroviral Therapy: Do They Age Faster?

Cited by 10 publications

References 85 publications

Transcriptomics age acceleration in prolonged treated HIV infection

Transcriptomics age acceleration in prolonged treated HIV infection

Epigenetic aging in older people living with HIV in Eswatini: a pilot study of HIV and lifestyle factors and epigenetic aging

Retinoic Acid Boosts HIV-1 Replication in MacrophagesviaCCR5/SAMHD1-Dependent and mTOR-Modulated Mechanisms

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