The role of CMV in HIV-associated accentuated aging
CMV 在 HIV 相关的加速衰老中的作用
基本信息
- 批准号:10760596
- 负责人:
- 金额:$ 67.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcquired Immunodeficiency SyndromeAcuteAdultAgeAgingAntigensAutomobile DrivingAutonomic DysfunctionB-LymphocytesBiological MarkersBiological Response ModifiersCD28 geneCD8-Positive T-LymphocytesCD8B1 geneCardiacCardiovascular PhysiologyChronicChronic DiseaseChronic Kidney FailureClinical TrialsCognitiveCognitive deficitsCollaborationsCoupledCytomegalovirusCytomegalovirus InfectionsDNADataDiseaseElderlyExhibitsFutureGeriatric AssessmentHIVHIV InfectionsHIV SeronegativityHyperlipidemiaHypertensionImmuneImmune responseImmunityImmunologic MarkersImpaired cognitionImpairmentIndividualIndustrializationInflammagingInflammationInflammation MediatorsInflammatoryLeadLifeLife ExpectancyLinkLongevityMalignant NeoplasmsMeasuresMediatingMental DepressionMotorMultivariate AnalysisNK Cell ActivationNatural Killer CellsNeutralization TestsNon-Insulin-Dependent Diabetes MellitusParticipantPersonsPharmacotherapyPhenotypePredictive ValuePremature aging syndromeProductionPublicationsQuality of lifeQuestionnairesRecording of previous eventsRoleSF-36SamplingSyndromeT-LymphocyteT-Lymphocyte SubsetsTestingTissuesUpper ExtremityVariantViralViral Load resultWorkage relatedantiretroviral therapycell motilitycognitive abilitycognitive functioncognitive testingcohortcomorbiditycytokinedisabilityexhaustionexperienceexperimental studyfallsfitnessfrailtyfunctional declinefunctional statushealthspanimmune functionimprovedinhibitorinsightmortalitymultimodalitymultiple chronic conditionsneutralizing antibodyprematureprospectiveresponsesensorseropositivesexsystemic inflammatory responsetoolvascular inflammation
项目摘要
ABSTRACT
Due to the introduction of combined antiretroviral therapy (ART), AIDS is now rare - instead HIV has
become a chronic disease in much of the industrial world. Persons over 50 with controlled HIV (PWH) make up
nearly half of all infected individuals (>0.6M people in the US alone) and their numbers are increasing. But
these people are not cured: PWH experience multiple comorbid conditions at rates higher than, and earlier in
life compared to, uninfected age-matched persons. These HIV-associated non-AIDS conditions (HANA) lead to
premature accumulation of physical and cognitive functional deficits that resemble a pronounced/ accelerated
aging phenotype. Inflammation and immune function decline accompany both HIV and aging, suggesting that
both could potentiate and/or drive aspects of exacerbated aging in PWH. Persistent cytomegalovirus (CMV)
infection has been implicated in immune aging and age-related inflammation too, but there are significant inter-
person variations and an incomplete understanding of control of CMV with aging. Limited data suggests that
the premature “aging” phenotype seen in PWH is only found in those co-infected with CMV, but the control of
CMV in PWH remains poorly understood. Therefore, CMV could be a driver of disabilities in older HIV+
individuals, a marker with stratifying and predictive value, or neither. We have developed a battery of tests to
measure CMV viral load, anti-CMV NK, T and B cell immunity, and concurrent levels of systemic inflammation,
and have found that while <50% of HIV-negative participants exhibit anti-CMV neutralizing Ab (nAb), >90%
HIV+ age-matched participants develop nAb. We hypothesize that anti-CMV nAb production is a direct function
of CMV load and replication during, and maybe also in the aftermath, of the acute HIV infection. We have also
developed and validated the upper extremity flexion (UEF) test that, coupled with cognitive testing, can provide
simultaneous assessment of frailty, motility, cardiovascular and cognitive function, all of which provide deep
functional insight into quality of life (QOL) and geriatric syndromes. We seek to use these tools to evaluate the
impact of CMV and CMV-associated inflammation as biomarkers in predicting trajectories of functional decline
in HIV+ individuals with aging. Our hypothesis is that PWH with signs of CMV reactivation (viral loads, high
levels of anti-CMV nAb, T and NK cell activation) experienced prolonged and high CMV reactivation during
acute HIV disease and/or in its aftermath, with a broad spectrum of immune and inflammatory abnormalities,
that predispose them for aggravated chronic conditions and geriatric syndromes such as frailty, mobility/falls
and reduced cognitive ability. We will test this hypothesis by multivariate analysis of immune and inflammatory
mediators and geriatric assessment in three observational (one prospective) and one anti-CMV drug treatment
cohort, including both sexes. This work will dissect the relationship between CMV, inflammation and reduced
overall fitness, frailty and accelerated and/or unsuccessful aging in HIV+ individuals and could provide basis
for broader anti-CMV treatment of older adults with HIV to improve their healthspan.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JANKO Z. NIKOLICH其他文献
JANKO Z. NIKOLICH的其他文献
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{{ truncateString('JANKO Z. NIKOLICH', 18)}}的其他基金
Mechanisms of age-related susceptibility to the chikungunya virus (CHIKV)
基孔肯雅病毒(CHIKV)与年龄相关的易感性机制
- 批准号:
10436970 - 财政年份:2018
- 资助金额:
$ 67.25万 - 项目类别:
Viral burden and systemic inflammation as biomarkers for chronic disease and frailty in aging
病毒负荷和全身炎症作为慢性疾病和衰老衰弱的生物标志物
- 批准号:
10153615 - 财政年份:2018
- 资助金额:
$ 67.25万 - 项目类别:
Mechanisms of age-related susceptibility to the chikungunya virus (CHIKV)
基孔肯雅病毒(CHIKV)与年龄相关的易感性机制
- 批准号:
10251001 - 财政年份:2018
- 资助金额:
$ 67.25万 - 项目类别:
Viral burden and systemic inflammation as biomarkers for chronic disease and frailty in aging
病毒负荷和全身炎症作为慢性疾病和衰老衰弱的生物标志物
- 批准号:
10412933 - 财政年份:2018
- 资助金额:
$ 67.25万 - 项目类别:
Thymic and peripheral Aspects of T cell Aging and Rejuvenation
T 细胞衰老和再生的胸腺和外周方面
- 批准号:
10226915 - 财政年份:2017
- 资助金额:
$ 67.25万 - 项目类别:
Project 4: Thymic and peripheral Aspects of T cell Aging and Rejuvenation
项目 4:T 细胞衰老和再生的胸腺和外周方面
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10226925 - 财政年份:2017
- 资助金额:
$ 67.25万 - 项目类别:
Peripheral T cell maintenance defects with aging
衰老导致外周 T 细胞维持缺陷
- 批准号:
10553995 - 财政年份:2017
- 资助金额:
$ 67.25万 - 项目类别:
Thymic and Peripheral Aspects of T Cell Aging and Rejuvenation
T 细胞衰老和再生的胸腺和外周方面
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10553988 - 财政年份:2017
- 资助金额:
$ 67.25万 - 项目类别:
Thymic and peripheral Aspects of T cell Aging and Rejuvenation
T 细胞衰老和再生的胸腺和外周方面
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9755287 - 财政年份:2017
- 资助金额:
$ 67.25万 - 项目类别:
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