Immune and metabolic dysfunction during aging in human cohorts
人类衰老过程中的免疫和代谢功能障碍
基本信息
- 批准号:10673299
- 负责人:
- 金额:$ 57.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-30 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAffectAgeAgingAnti-Inflammatory AgentsAutoimmune DiseasesBiologicalBiological MarkersBloodBrainCellsClinicalCommunitiesComplementContainmentCross-Sectional StudiesDefectDiabetes MellitusDiagnosisElderlyEnrollmentEventExposure toFailureFoundationsFunctional disorderFutureGeneticGoalsGrowthHIVHealthHealth systemHigh PrevalenceHispanicHomeostasisHumanImmuneImmune System DiseasesImmunologicsImpairmentIndividualInfectionInflammationInterventionJointsLeadLongitudinal StudiesLungLung infectionsMeasuresMetabolicMetabolic dysfunctionMetabolismMexicoMitochondriaModelingMolecularMorbidity - disease rateMusMycobacterium tuberculosisNon-Insulin-Dependent Diabetes MellitusOrgan failureOutcomeOxidative StressOxidative Stress PathwayParticipantPathway interactionsPatientsPersonsPhenotypePlasmaPremature aging syndromeProcessProteinsPulmonary TuberculosisResearch PersonnelRoleSamplingSiteSkeletal MuscleSpecimenTestingTexasTimeTuberculosisWaste Managementage effectage groupbody systemchemokinecohortcytokinefunctional declinehealthspanhigh riskhuman old age (65+)immune functionin vivo monitoringmonocytemortalitynovelolder patientoxidationpathogenpreventresearch clinical testingresponserestorationtherapy developmenttuberculosis treatment
项目摘要
Old age is associated with a high prevalence of metabolic alterations like type 2 diabetes mellitus (DM) and preOM 0ointly 'dysglycemia'), and with an immunologic decline associated with higher risk of developing and dying
from lung infections like pulmonary tuberculosis (PTB). These immune-metabolic alterations are accompanied
by failure in other organ systems (lung, brain, skeletal muscle), leading to increased morbidity and mortality.
Understanding these interactions and detecting them early is critical for delaying, preventing or restoring an
individual's organ system health. The underlying mechanisms for immunometabolic alterations are unknown, but
our joint studies in humans and mice with and without Mycobacterium tuberculosis (M.tb) infection provide
support for the role of oxidative stress and associated inflammation as a driver. Accordingly, in our Hispanic
human cohort, we find that systemic oxidative stress is higher in TB or DM patients, and exacerbates age effects.
We hypothesize that aging-related immunometabolic changes that drive organ failure are largely originated from
impaired mitochondria-driven oxidative stress pathways. We will test these hypotheses, conducting snap-shot
and longitudinal studies in humans. We will identify the age at which these changes initiate and the most affected
pathway, focusing on monocytes attained from relatively non-invasive specimens. i.e., blood. These studies will
take advantage of a well-defined Hispanic clinical cohort at the Texas-Mexico border and our established team
of field investigators. In Aim 1, we will determine: i) when altered measures of mitochondria-induced oxidative
stress and immune dysfunction are first detected in blood and monocytes during the process of aging, to identify
the most effective age for interventions. In Aim 2, we will determine the impact of host biological perturbations
(dysglycemia and PTB) on these outcomes. We will further evaluate if PTB may serve as a new model of
accelerated aging, given its association with inflammation and oxidative stress. Overall, results will provide the
foundation for future clinical testing selected interventions in-vivo and monitoring individualized responsiveness
with simple biomarker testing, to promote extended cellular health and organ system healthspan.
老年与代谢改变如2型糖尿病(DM)和前OM(又称“血糖异常”)的高患病率相关,并且与免疫功能下降相关,免疫功能下降与更高的发展和死亡风险相关
肺结核等肺部感染。这些免疫代谢变化是伴随着的
其他器官系统(肺、脑、骨骼肌)衰竭,导致发病率和死亡率增加。
了解这些相互作用并及早发现它们对于延迟、预防或恢复疾病至关重要。
个人的器官系统健康。免疫代谢改变的潜在机制尚不清楚,但
我们在有和没有结核分枝杆菌(M.tb)感染的人类和小鼠中的联合研究提供了
支持氧化应激和相关炎症作为驱动因素的作用。因此,在我们的西班牙裔
在人类队列中,我们发现TB或DM患者的全身氧化应激更高,并加剧了年龄效应。
我们假设,与衰老相关的免疫代谢变化,驱动器官衰竭,主要是源于
受损的氧化应激途径。我们将测试这些假设,进行快照
和人类的纵向研究。我们将确定这些变化开始的年龄和受影响最大的年龄
途径,重点是从相对非侵入性标本中获得的单核细胞。也就是说,血这些研究将
利用德克萨斯州-墨西哥边境定义明确的西班牙裔临床队列和我们的既定团队
现场调查员。在目标1中,我们将确定:i)当改变的措施,
在衰老过程中,首先在血液和单核细胞中检测到应激和免疫功能障碍,
最有效的干预年龄。在目标2中,我们将确定宿主生物扰动的影响
(精神障碍和PTB)对这些结果的影响。我们将进一步评估PTB是否可以作为一种新的模式,
加速衰老,因为它与炎症和氧化应激有关。总的来说,结果将提供
为未来的临床试验奠定了基础选定的干预措施在体内和监测个性化的反应
通过简单的生物标志物检测,促进细胞健康和器官系统健康。
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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{{ truncateString('BLANCA I RESTREPO', 18)}}的其他基金
Improving rapid phenotypic drug susceptibility testing for drug resistant tuberculosis in high-burden areas
完善高负担地区耐药结核病快速表型药敏检测
- 批准号:
10658013 - 财政年份:2023
- 资助金额:
$ 57.45万 - 项目类别:
Immune and metabolic dysfunction during aging in human cohorts
人类衰老过程中的免疫和代谢功能障碍
- 批准号:
10707456 - 财政年份:2022
- 资助金额:
$ 57.45万 - 项目类别:
Altered immune-endocrine axis in type 2 diabetes and tuberculosis risk
2 型糖尿病和结核病风险中免疫内分泌轴的改变
- 批准号:
9011503 - 财政年份:2015
- 资助金额:
$ 57.45万 - 项目类别:
Uncontrolled diabetes, immune dysregulation and tuberculosis
不受控制的糖尿病、免疫失调和结核病
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7661731 - 财政年份:2009
- 资助金额:
$ 57.45万 - 项目类别:
Uncontrolled diabetes, immune dysregulation and tuberculosis
不受控制的糖尿病、免疫失调和结核病
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7905082 - 财政年份:2009
- 资助金额:
$ 57.45万 - 项目类别:
Rapid characterization of mycobacteria and drug resistance in paucibacillary TB
少杆菌结核病中分枝杆菌和耐药性的快速鉴定
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7268101 - 财政年份:2006
- 资助金额:
$ 57.45万 - 项目类别:
Rapid characterization of mycobacteria and drug resistance in paucibacillary TB
少杆菌结核病中分枝杆菌和耐药性的快速鉴定
- 批准号:
7104475 - 财政年份:2006
- 资助金额:
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