Thymic and Peripheral Aspects of T Cell Aging and Rejuvenation
Thymic and Peripheral Aspects of T Cell Aging and Rejuvenation
批准号:
10553988
负责人:
JANKO Z. NIKOLICH
金额:
$271.3万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
未结题
起止时间:
2017-09-15 至 2028-02-29
关键词:
2019-nCoVAddressAffectAgeAgingArchivesAutoimmune DiseasesAutoimmunityBone MarrowCOVID-19 pandemicCell AgingCell CountCell MaintenanceCell SurvivalCell physiologyCellsCommunicable DiseasesCommunicationData ScienceDefectDeteriorationDissectionEconomic BurdenEconomicsElderlyElementsEventFailureGene Expression ProfilingGenetic ModelsGoalsHealthHealthcareHumanImmuneImmune responseImmune systemImmunityImmunologicsImpairmentIndividualInfectionInfectious AgentInformaticsInjuryInterventionKnowledgeLaboratoriesLengthLifeLongevityMaintenanceMalignant NeoplasmsModalityMolecularMonitorMusNatural regenerationOutputPathway interactionsPeripheralPhenotypePre-Clinical ModelProcessProductionQuality of lifeReagentRegenerative capacityRejuvenationResearchRoleSamplingSavingsScienceSelf ToleranceSignal TransductionSocietiesSpleenStandardizationStatistical Data InterpretationT-Cell DevelopmentT-LymphocyteTestingTherapeuticThymus GlandTranslatingTranslationsVirusage relatedagedanimal tissuecentral tolerancecomparativedata sharingdesigneffective interventionexperiencehealthspanhigh throughput analysisimmune functionimmune system functionimmunosenescenceimprovedlymph nodeslymphoid organmortalitymouse modelneoplastic cellnovelperipheral lymphoid organprimary lymphoid organprogramsresponsesecondary lymphoid organsuccesssynergismtimeline
中文摘要
整体——抽象
英文摘要
OVERALL- Abstract
Infectious disease, cancer, and autoimmune disorders affect hundreds of millions of older adults. They
reduce length and quality of life across the globe and inflict a massive economic burden on society, as vividly
exemplified by the SARS-CoV-2 pandemic, that has claimed 93.1% of its victims amongst those 50 years and
older, and 74.4% in those 64 and older. Yet, despite decades of research, restoring protective immunity in
older adults has remained elusive. One critical factor contributing to age-related immune decline is a loss of
naïve T (Tn) cell numbers and function, and their rejuvenation is highly desirable in order to enhance protective
immunity and overall healthspan in older adults.
The renewal of this T cell Rejuvenation Program Project is centered on two key questions: (1) why do Tn
cell numbers and function deteriorate with age; and (2) what can be done about it? The premise of the program
is that Tn cell aging is multifactorial and that it can only be resolved by targeting multiple defects. Thymic
involution and the resulting decline in T cell production is the earliest event leading to immunosenescence.
This reduction is compounded by a decline in bone marrow function, as well as by defects in Tn cell
maintenance and function in the periphery. These deficiencies combine to erode the ability of the older immune
system to detect and eliminate infectious agents and neoplastic cells, and to properly guard against
autoimmunity. In the first program period, we strongly confirmed our initial hypotheses that lymphoid organ
stromal elements deteriorate earlier than previously thought, and in a manner to decisively erode immunity,
with aging. We will build on the synergy and success of the initial program period, where discoveries in one
project are critically informing science in others, and continue to identify mechanistic reasons behind reduced
central and peripheral lymphoid organ function with aging. We will then develop combined strategies to
ameliorate these defects to improve immune defense in the elderly. Our hypothesis is that mechanistic
dissection of defects in both thymic production AND peripheral Tn cell maintenance is required to devise and
test effective interventions for T cell rejuvenation in the elderly.
Three integrated projects led by experts in the field, supported by four cutting-edge cores, will test this
hypothesis and achieve the following Program Goals: 1. Define mechanistic changes in primary and secondary
lymphoid organ aging; 2. Determine the endogenous regenerative capacity of thymic and secondary lymphoid
organ stroma over the lifespan; 3. Relate the progression of murine thymus, lymph node (LN) and T cell aging
phenotypes to humans; and 4. Devise and test rejuvenation strategies to improve thymopoiesis, T cell survival
and peripheral T cell maintenance and function, so as to enhance protective immunity.
Over this support period, the above goals will provide a wealth of basic knowledge that will be translated to
preclinical models and be poised for translation to older adults.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
The role of CMV in HIV-associated accentuated aging
-
批准号:10760596
-
项目类别:
-
资助金额:$67.25万
-
财政年份:2023
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Mechanisms of age-related susceptibility to the chikungunya virus (CHIKV)
-
批准号:10436970
-
项目类别:
-
资助金额:$33.77万
-
财政年份:2018
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Viral burden and systemic inflammation as biomarkers for chronic disease and frailty in aging
-
批准号:10153615
-
项目类别:
-
资助金额:$65.25万
-
财政年份:2018
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Mechanisms of age-related susceptibility to the chikungunya virus (CHIKV)
-
批准号:10251001
-
项目类别:
-
资助金额:$33.77万
-
财政年份:2018
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Viral burden and systemic inflammation as biomarkers for chronic disease and frailty in aging
-
批准号:10412933
-
项目类别:
-
资助金额:$64.92万
-
财政年份:2018
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Thymic and peripheral Aspects of T cell Aging and Rejuvenation
-
批准号:10226915
-
项目类别:
-
资助金额:$192.44万
-
财政年份:2017
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Project 4: Thymic and peripheral Aspects of T cell Aging and Rejuvenation
-
批准号:10226925
-
项目类别:
-
资助金额:$35.08万
-
财政年份:2017
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Peripheral T cell maintenance defects with aging
-
批准号:10553995
-
项目类别:
-
资助金额:$53.06万
-
财政年份:2017
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Scientific Integration and Administration
-
批准号:10553989
-
项目类别:
-
资助金额:$15.63万
-
财政年份:2017
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Thymic and peripheral Aspects of T cell Aging and Rejuvenation
-
批准号:9755287
-
项目类别:
-
资助金额:$198.99万
-
财政年份:2017
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Core A Scientific and Administrative Integration: Thymic and peripheral Aspects of T cell Aging and Rejuvenation
-
批准号:10226916
-
项目类别:
-
资助金额:$12.2万
-
财政年份:2017
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Disparities in Immune Fitness in HIV+ Subjects with Aging
-
批准号:9203464
-
项目类别:
-
资助金额:$18.6万
-
财政年份:2016
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Mechanisms of age-related susceptibility to the chikungunya virus (CHIKV)
-
批准号:9350814
-
项目类别:
-
资助金额:$38.38万
-
财政年份:2016
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Longevity extension and immune function in aging (R21)
-
批准号:8842072
-
项目类别:
-
资助金额:$17.74万
-
财政年份:2014
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
IMPACT OF CMV UPON T-CELL AGING AND IMMUNE DEFENSE
-
批准号:9068437
-
项目类别:
-
资助金额:$14.31万
-
财政年份:2014
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
IMPACT OF CMV UPON T-CELL AGING AND IMMUNE DEFENSE
-
批准号:9269947
-
项目类别:
-
资助金额:$50.15万
-
财政年份:2014
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
IMPACT OF CMV UPON T-CELL AGING AND IMMUNE DEFENSE
-
批准号:9060874
-
项目类别:
-
资助金额:$45.62万
-
财政年份:2014
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Impact of CMV Upon T-Cell Aging and Immune Defense
-
批准号:9480499
-
项目类别:
-
资助金额:$6.68万
-
财政年份:2014
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
Longevity extension and immune function in aging (R21)
-
批准号:8699982
-
项目类别:
-
资助金额:$22.08万
-
财政年份:2014
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
IMPACT OF CMV UPON T-CELL AGING AND IMMUNE DEFENSE
-
批准号:8891346
-
项目类别:
-
资助金额:$43.48万
-
财政年份:2014
-
负责人:JANKO Z. NIKOLICH
-
依托单位:
海外基金