Acceleration of Circulatory and Neurological Aging due to Wildfire Exposures
野火暴露导致循环系统和神经系统老化加速
基本信息
- 批准号:10544543
- 负责人:
- 金额:$ 75.65万
- 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:2022-01-01 至 2026-12-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcuteAgeAgingAlzheimer&aposs DiseaseAmyloidAmyloid beta-ProteinAnimalsAnti-Inflammatory AgentsAstrocytesAtherosclerosisAttenuatedBloodBlood - brain barrier anatomyBlood VesselsBrainCD36 geneCardiovascular systemCellsChronicChronic DiseaseCirculationComplexComplex MixturesDementiaDisastersDiseaseDisease MarkerElderlyEndothelial CellsEndotheliumEnvironmentEnvironmental ExposureEnvironmental PollutantsEnvironmental Risk FactorEtiologyEventExposure toGasesGeneticHealthHistopathologyHumanImpairmentInflammationInflammatoryInhalationLaboratoriesLifeLigandsLongevityLungMatrix MetalloproteinasesMediatorMetabolicMetabolismMetalloproteasesMicrogliaMolecularNeurologicNeurological outcomeOutcomeOzoneParticulatePathogenesisPathogenicityPathologyPathway interactionsPeptide FragmentsPeptide HydrolasesPeptidesPhenotypePopulationPredispositionProcessProtein FragmentProteinsProteomeProteomicsReceptor CellResearchResveratrolRoleSIRT1 geneSerpinsSerumSmokeStructureSystemTestingTherapeutic UsesToxicologyUnited StatesUp-RegulationVascular Cell Adhesion Molecule-1Vascular DiseasesVascular Endothelial CellWildfireage relatedbiomass fuelcerebrovascularenvironmental stressorexperienceextreme weatherglial activationhealthspanimprovedin vivolung injurymouse modelmultiple omicsneuralneuroinflammationneurological pathologyneuropathologypathological agingpharmacologicpollutantreceptorrecruitresponsesecretory proteinsenescencetau Proteinstherapeutic targettoxicantwood smoke
项目摘要
SUMMARY: Acceleration of Circulatory and Neurological Aging due to Wildfire Exposures
Wildfires pose an increasing threat to a growing and aging global population, notably in the Western United
States. Little is known about the influence of inhaled environmental pollutants, such as from wildfire smoke
(WFS) exposure, on molecular pathways governing cerebrovascular and neurological aging in the etiology of
Alzheimer’s disease (AD) and dementia. Yet, parallel molecular changes are induced by aging and inhaled
toxicants within the blood, raising the potential for their negative interaction. This includes increased
metalloproteinases, serpins and inflammatory factors that can directly promote age-related neurological
pathologies. Moreover, our research documents how inhaled pollutants cause blood compositional changes,
particularly as protease-induced peptides, that promote vascular dysfunction and neurological inflammation.
Inhaled toxicant induced circulating factors promote blood-brain barrier (BBB) permeation, glial activation and
pro-inflammatory secretion and recruitment, and elevation of AD markers such as amyloid beta. Inhaled
toxicant and age-related BBB deficits and associated sequelae show common involvement for vascular cell
adhesion molecule-1 (VCAM-1), which is directly increased on cerebrovascular endothelial cells following
exposure to WFS. Thus, we hypothesize that WFS augments pathological aging outcomes of senescence-
associated secretory proteins in the circulating milieu to advance BBB compromise, neuroinflammation, and
prime AD pathogenesis principally through expression/activity of cerebrovascular VCAM-1. To test this
hypothesis, our team proposes the following aims: 1. Assess interaction between WFS exposure-induced and
aging-related circulatory changes as drivers of BBB impairment, neuroinflammation, and early evidence of
amyloid and tau proteinopathy. Serum compositional changes caused by aging x WFS exposure will be
comprehensively assessed at the protein, peptide and metabolite levels and paired with in vivo histopathology
and functional ex vivo phenotyping of major hallmarks of neurological and cardiovascular aging. 2. Delineate
the role of cerebrovascular endothelial receptors, namely CD36, as intermediates in WFS-induced
neuroinflammation. CD36 is clearly involved in acute responses of the BBB to inhaled toxicants, and likely to
upregulation of VCAM-1, which has been recently implicated as a mediator of aging-related neurological
sequelae. 3. Pharmacologically attenuate accelerated aging from WFS exposure using a sirtuin-1 activator
(resveratrol) with an NAD+ booster (NMN) and/or a senolytic cocktail to reduce aging-related circulating
factors. These permutations will target the key outcomes of circulatory changes from WFS exposure in target
cells (vascular, neural) to reduce early pro-AD pathogenic BBB compromise, neuroinflammation and
proteinopathy related outcomes. Together, findings will detail the influence of WFS in advancing age-related
AD pathogenesis by generating vascular-compromising and glial-stimulating factors in the circulation, and
evaluate counteracting therapeutics for use following unavoidable WFS exposure.
摘要:野火暴露导致循环和神经系统老化加速
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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Matthew J Campen其他文献
Bioaccumulation of Microplastics in Decedent Human Brains Assessed by Pyrolysis Gas Chromatography-Mass Spectrometry
通过热解气相色谱-质谱法评估死者大脑中微塑料的生物累积
- DOI:
10.21203/rs.3.rs-4345687/v1 - 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Matthew J Campen;Alex Nihart;Marcus A Garcia;Rui Liu;Marian Olewine;Eliseo F Castillo;Barry Bleske;Justin Scott;Tamara Howard;Jorge Gonzalez;Natalie Adolphi;Daniel F Gallego;E. Hayek - 通讯作者:
E. Hayek
Matthew J Campen的其他文献
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{{ truncateString('Matthew J Campen', 18)}}的其他基金
13th International Particle Toxicology Meeting
第13届国际粒子毒理学会议
- 批准号:
10540585 - 财政年份:2022
- 资助金额:
$ 75.65万 - 项目类别:
Acceleration of Circulatory and Neurological Aging due to Wildfire Exposures
野火暴露导致循环系统和神经系统老化加速
- 批准号:
10363056 - 财政年份:2022
- 资助金额:
$ 75.65万 - 项目类别:
University of New Mexico Center for Metals in Biology and Medicine
新墨西哥大学生物和医学金属中心
- 批准号:
10629336 - 财政年份:2020
- 资助金额:
$ 75.65万 - 项目类别:
SARS-CoV-2 Genomic Surveillance and Epidemiology in New Mexico
新墨西哥州 SARS-CoV-2 基因组监测和流行病学
- 批准号:
10381051 - 财政年份:2020
- 资助金额:
$ 75.65万 - 项目类别:
University of New Mexico Center for Metals in Biology and Medicine
新墨西哥大学生物和医学金属中心
- 批准号:
10408025 - 财政年份:2020
- 资助金额:
$ 75.65万 - 项目类别:
SARS-CoV-2 Genomic Surveillance and Epidemiology in New Mexico
新墨西哥州 SARS-CoV-2 基因组监测和流行病学
- 批准号:
10594348 - 财政年份:2020
- 资助金额:
$ 75.65万 - 项目类别:
University of New Mexico Center for Metals in Biology and Medicine
新墨西哥大学生物和医学金属中心
- 批准号:
10202647 - 财政年份:2020
- 资助金额:
$ 75.65万 - 项目类别:
New Mexico Center for Metals in Biology and Medicine - Equipment Supplement
新墨西哥生物和医学金属中心 - 设备补充
- 批准号:
10395875 - 财政年份:2020
- 资助金额:
$ 75.65万 - 项目类别:
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