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 2 型糖尿病 (DM) 和 preOM 0(即“血糖异常”)等代谢改变的高发生率有关,并且与免疫功能下降有关,而免疫功能下降则与较高的发病和死亡风险相关
肺部感染,如肺结核 (PTB)。这些免疫代谢改变伴随着
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
个人器官系统的健康。免疫代谢改变的潜在机制尚不清楚,但
我们对感染或未感染结核分枝杆菌 (M.tb) 的人类和小鼠进行的联合研究提供了
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,我们发现结核病或糖尿病患者的全身氧化应激更高,并加剧了年龄效应。
我们假设导致器官衰竭的衰老相关免疫代谢变化很大程度上源于
线粒体驱动的氧化应激途径受损。我们将测试这些假设,进行快照
和人类纵向研究。我们将确定这些变化开始的年龄以及受影响最严重的人
途径,重点关注从相对非侵入性标本中获得的单核细胞。即血液。这些研究将
利用德克萨斯州-墨西哥边境明确的西班牙裔临床队列和我们现有的团队
的实地调查员。在目标 1 中,我们将确定:i) 何时改变线粒体诱导的氧化测量
在衰老过程中,首先在血液和单核细胞中检测到压力和免疫功能障碍,以识别
干预措施最有效的年龄。在目标 2 中,我们将确定宿主生物扰动的影响
(血糖异常和 PTB)对这些结果的影响。我们将进一步评估PTB是否可以作为新的模式
鉴于其与炎症和氧化应激的相关性,加速衰老。总体而言,结果将提供
为未来临床测试选定的体内干预措施和监测个体化反应奠定基础
通过简单的生物标志物测试,促进延长细胞健康和器官系统健康寿命。
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
- 批准号:
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
- 批准号:
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:
$ 57.45万 - 项目类别:
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