Adult epigenetics and telomere length in relation to improved nutrition in early life
成人表观遗传学和端粒长度与改善早期营养有关
基本信息
- 批准号:10562425
- 负责人:
- 金额:$ 67.34万
- 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:2023-03-15 至 2028-01-31
- 项目状态:未结题
- 来源:
- 关键词:2 year old3 year oldAddressAdultAffectAgeAge MonthsAge YearsAgingAnthropometryBiological AgingBiological AssayBiological MarkersBody mass indexCentral AmericaCessation of lifeChildChild MalnutritionChinaChronologyCollaborationsConceptionsCountryDNADNA MethylationData CollectionDevelopmentDiabetes MellitusDietDietary InterventionDiseaseElderlyEnrollmentEnvironmentEpigenetic ProcessExposure toFaceFaminesFreezingGoalsGuatemalaHealthHeightHumanIncidenceIncomeIndividualInfantInterventionIntervention TrialLengthLeukocytesLifeLife Cycle StagesLife ExpectancyLinkLongevityLongitudinal StudiesMalnutritionMeasuresMendelian randomizationMetabolicNetherlandsNutrition IndexesNutritional StudyNutritional statusOutcomePanamaPaperParticipantPathway interactionsPatternPersonsPhysiologicalPregnancyPregnant WomenPremature aging syndromePrenatal NutritionPreventionPrevention strategyProductivityProspective, cohort studyProteinsPublishingRandomizedRecording of previous eventsResearchResearch InstituteResearch PersonnelResource-limited settingRisk FactorsRoleSamplingSiteStrategic PlanningSubgroupSupplementationTreatment ProtocolsUnited States National Institutes of HealthUniversitiesadverse outcomecandidate markercohortdesigndiabetes riskearly childhoodearly-life nutritioneffectiveness evaluationepigenome-wide association studiesexperiencefollow-uphealthspanhealthy aginghigh body mass indeximprovedindexinginnovationintergenerationallow and middle-income countriesmethylation patternmodifiable riskmultidisciplinarynovelnutritionnutritional supplementationoffspringprematurepreventpublic health relevancestressortelomere
项目摘要
Project Abstract / Summary
Our broad goal is to reduce the consequences caused by premature aging through addressing key research
gaps that represent challenges to more effective mitigation efforts, particularly in low- and middle-income
countries. Our central working hypothesis is that optimal early-life nutrition reduces physiologic aging, specifically
via persistent impacts on DNA-related mechanisms (DNA methylation [DNAm], telomere length) over the human
life course. The rationale extends key previous findings from the study team, particularly that (1) gestational
exposure to the Dutch famine resulted in observable epigenetic differences in adulthood; (2) telomere length of
infants and children differ by early-life maternal factors and metabolic indicators; and (3) exposure to a nutrition
supplementation intervention led to reduced diabetes incidence at age 37-52 y. We have been following a unique
cohort of individuals who participated as children in a nutrition supplementation intervention trial conducted in
four villages in Guatemala from 1969 to 1977. We define full intervention exposure as the first 1,000 days of life
between conception and two years of age; participants with full exposure will be compared to those with partial
(0-999 of these ‘first 1,000 days’) and no intervention exposure. In this study, we propose to extract DNA from
frozen buffy coats collected between 2015-2017 from these now-adult cohort participants (n=1,139). We will
assay samples for DNAm and leukocyte telomere length, which are two mammalian aging hallmarks. In Aim 1,
we will evaluate the impact of nutrition supplementation during the first 1,000 days on DNAm patterns and DNAm-
calculated epigenetic age, including PhenoAge and other epigenetic clocks. We will also further examine CpG
sites associated with early-life nutrition exposure with Mendelian randomization to assess causal associations
with diabetes or BMI. In Aim 2, we will determine whether (1) nutrition supplementation during the first 1,000
days, and (2) life course nutritional status trajectories are associated with longer leukocyte telomere length. This
innovative study will be an opportunity to examine the effectiveness of an actionable early-life nutrition
intervention on the human health span. It will be the first epigenome-wide association study utilizing Mendelian
randomization to assess early-life nutrition supplementation and adult metabolic outcomes to our knowledge. If
successful, this study has the potential to identify novel subclinical physiologic aging indices that are nutrition-
sensitive, which could lead to better intervention impact assessment and prevention strategies for premature
aging. This innovative, multidisciplinary study is optimally suited to answer profound questions relating to early-
life determinants of the human health span in adulthood. It builds upon extensive (>50y) and productive (>300
published papers) experience with this cohort, and a successful history of collaboration among experienced and
productive researchers at Emory University, the Institute of Central America and Panama, and Vitalant Research
Institute.
项目摘要/总结
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('ARYEH DAVID STEIN', 18)}}的其他基金
Early childhood nutrition and adult metabolomic and cardiometabolic profiles
幼儿营养和成人代谢组学和心脏代谢特征
- 批准号:
9058129 - 财政年份:2014
- 资助金额:
$ 67.34万 - 项目类别:
Early childhood nutrition and adult metabolomic and cardiometabolic profiles
幼儿营养和成人代谢组学和心脏代谢特征
- 批准号:
9254217 - 财政年份:2014
- 资助金额:
$ 67.34万 - 项目类别:
Early childhood nutrition and adult metabolomic and cardiometabolic profiles
幼儿营养和成人代谢组学和心脏代谢特征
- 批准号:
8630478 - 财政年份:2014
- 资助金额:
$ 67.34万 - 项目类别:
Education and Health Across the Life course in Guatemala
危地马拉终生教育和健康
- 批准号:
7007346 - 财政年份:2004
- 资助金额:
$ 67.34万 - 项目类别:
Education and Health Across the Life course in Guatemala
危地马拉终生教育和健康
- 批准号:
6736658 - 财政年份:2004
- 资助金额:
$ 67.34万 - 项目类别:
Education and Health Across the Life course in Guatemala
危地马拉终生教育和健康
- 批准号:
6849299 - 财政年份:2004
- 资助金额:
$ 67.34万 - 项目类别:
Zinc, Mental Health and School Performance in Mexico
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- 批准号:
7233666 - 财政年份:2004
- 资助金额:
$ 67.34万 - 项目类别:
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