Distinct Intestinal Microbial Signatures Linked to Accelerated Biological Aging in People with HIV
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PROVIDER: PRJNA1030392 | ENA |
REPOSITORIES: ENA
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Project description:Genome-wide DNA methylation profiling of colon and ileal biopsies, blood samples from people living with HIV on ART and their matched HIV-negative counterparts. Despite having similar chronological ages, PWH on ART exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to HIV-negative controls. Investigating the relationship between microbial translocation and biological aging, PWH on ART had decreased levels of tight junction proteins in the colon and ileum, along with increased microbial translocation.
2024-02-28 | GSE245924 | GEO
Project description:People living with HIV (PLWH) experience increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors associated with this vulnerability remain uncertain. In the general population, alterations in the N-glycans on IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG N-glycans in cross-sectional and longitudinal samples from 1,214 women and men, living with and without HIV. PLWH exhibit an accelerated accumulation of pro-aging-associated glycan alterations and heightened expression of senescence-associated glycan-degrading enzymes compared to controls. These alterations correlate with elevated markers of inflammation and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit a reduced ability to elicit anti-HIV Fc-mediated immune activities. These findings hold potential for the development of biomarkers and tools to identify and prevent premature aging and comorbidities in PLWH.
2024-03-20 | GSE254483 | GEO
Project description:People with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1,216 women and men, both living with virally suppressed HIV and those without HIV. Our glycan-based machine learning models indicate that living with chronic HIV significantly accelerates the accumulation of pro-aging associated glycomic alterations. Consistently, PWH exhibit heightened expression of senescence associated glycan-degrading enzymes compared to their controls. These glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit reduced anti-HIV IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.
2024-03-21 | PXD046510 | Pride
Project description:Immunoglobulin G N-glycan Markers of Accelerated Biological Aging During Chronic HIV Infection
| PRJNA1070656 | ENA
Project description:In this study we performed data-independet mass-spectrometry analysis of blood plasma collected from a cohort consisting of people living with HIV-1, people living with HIV-2, and HIV seronegative individuals. The data was used to infer signs of damage to a wide array of tissues and cell types.
2024-02-16 | PXD045155 | Pride
Project description:BackgroundPeople living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed to intestinal microbial dysbiosis and translocation, which may lead to non-AIDS-related aging-associated comorbidities. The extent to which living with HIV - influenced by the infection itself, ART usage, sexual orientation, or other associated factors - affects the biological age of the intestines is unclear. Furthermore, the role of microbial dysbiosis and translocation in the biological aging of PLWH remains to be elucidated. To investigate these uncertainties, we used a systems biology approach, analyzing colon and ileal biopsies, blood samples, and stool specimens from PLWH on ART and people living without HIV (PLWoH) as controls.ResultsPLWH exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to PLWoH. Investigating the relationship between microbial translocation and biological aging, PLWH had decreased levels of tight junction proteins in the intestines, along with increased microbial translocation. This intestinal permeability correlated with faster biological aging and increased inflammation. When investigating the relationship between microbial dysbiosis and biological aging, the intestines of PLWH had higher abundance of specific pro-inflammatory bacteria, such as Catenibacterium and Prevotella. These bacteria correlated with accelerated biological aging. Conversely, the intestines of PLWH had lower abundance of bacteria known for producing the anti-inflammatory short-chain fatty acids, such as Subdoligranulum and Erysipelotrichaceae, and these bacteria were associated with slower biological aging. Correlation networks revealed significant links between specific microbial genera in the colon and ileum (but not in feces), increased aging, a rise in pro-inflammatory microbe-related metabolites (e.g., those in the tryptophan metabolism pathway), and a decrease in anti-inflammatory metabolites like hippuric acid.ConclusionsWe identified specific microbial compositions and microbiota-related metabolic pathways that are intertwined with intestinal and systemic biological aging. This microbial signature of biological aging is likely reflecting various factors including the HIV infection itself, ART usage, sexual orientation, and other aspects associated with living with HIV. A deeper understanding of the mechanisms underlying these connections could offer potential strategies to mitigate accelerated aging and its associated health complications. Video Abstract.
| S-EPMC10882811 | biostudies-literature
Project description:A growing literature suggests a relationship between HIV-infection and a molecular profile of age acceleration. However, despite the widely known high prevalence of HIV-related brain atrophy and HIV-associated neurocognitive disorder (HAND), epigenetic age acceleration has not been linked to HIV-related changes in structural MRI. We applied morphological MRI methods to study the brain structure of 110 virally suppressed participants with HIV infection and 122 uninfected controls age 22-72. All participants were assessed for cognitive impairment, and blood samples were collected from a subset of 86 participants with HIV and 83 controls to estimate epigenetic age. We examined the group-level interactive effects of HIV and chronological age and then used individual estimations of epigenetic age to understand the relationship between age acceleration and brain structure. Finally, we studied the effects of HAND. HIV-infection was related to gray matter reductions, independent of age. However, using epigenetic age as a biomarker for age acceleration, individual HIV-related age acceleration was associated with reductions in total gray matter. HAND was associated with decreases in thalamic and hippocampal gray matter. In conclusion, despite viral suppression, accentuated gray matter loss is evident with HIV-infection, and greater biological age acceleration specifically relates to such gray matter loss.
| S-EPMC8258439 | biostudies-literature
Project description:People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular disease (ASCVD). Proportions of vascular homing monocytes are enriched in PWH; however, little is known regarding monocyte-derived macrophages (MDMs) that may drive atherosclerosis in this population. We isolated PBMCs from people with and without HIV, and cultured these cells for 5 days in medium containing autologous serum to generate MDMs. Differential gene expression (DGE) analysis of MDMs from PWH identified broad alterations in innate immune signaling (IL-1β, TLR expression, PPAR βδ) and lipid processing (LXR/RXR, ACPP, SREBP1). Transcriptional changes aligned with the functional capabilities of these cells. Expression of activation markers and innate immune receptors (CD163, TLR4, and CD300e) was altered on MDMs from PWH, and these cells produced more TNFa, reactive oxygen species (ROS), and matrix metalloproteinases (MMPs) than did cells from people without HIV. MDMs from PWH also had greater lipid accumulation and uptake of oxidized LDL. PWH had increased serum levels of free fatty acids (FFAs) and ceramides, with enrichment of saturated FAs and a reduction in polyunsaturated FAs. Levels of lipid classes and species that are associated with CVD correlated with unique DGE signatures and altered metabolic pathway activation in MDMs from PWH. Here, we show that MDMs from PWH display a pro-atherogenic phenotype; they readily form foam cells, have altered transcriptional profiles, and produce mediators that likely contribute to accelerated ASCVD.
2020-10-22 | GSE157884 | GEO
Project description:Stress triggers anticipatory physiological responses that promote survival, a phenomenon termed allostasis. However, the chronic activation of energy-dependent allostatic responses results in allostatic load, a dysregulated state that predicts functional decline, accelerates aging, and increases mortality in humans. The energetic cost and cellular basis for the damaging effects of allostatic load have not been defined. Here, by longitudinally profiling three unrelated primary human fibroblast lines across their lifespan, we find that chronic glucocorticoid exposure increases cellular energy expenditure by ∼60%, along with a metabolic shift from glycolysis to mitochondrial oxidative phosphorylation (OxPhos). This state of stress-induced hypermetabolism is linked to mtDNA instability, non-linearly affects age-related cytokines secretion, and accelerates cellular aging based on DNA methylation clocks, telomere shortening rate, and reduced lifespan. Pharmacologically normalizing OxPhos activity while further increasing energy expenditure exacerbates the accelerated aging phenotype, pointing to total energy expenditure as a potential driver of aging dynamics. Together, our findings define bioenergetic and multi-omic recalibrations of stress adaptation, underscoring increased energy expenditure and accelerated cellular aging as interrelated features of cellular allostatic load.
| S-EPMC10528419 | biostudies-literature