Genetic Determinants of Human Transcriptional Aging

人类转录衰老的遗传决定因素

基本信息

项目摘要

DESCRIPTION (provided by applicant): Age effects in humans are observed at all levels of organization from molecular pathways to organ systems. While there is substantial evidence that genetic variation influences the rate at which aging occurs, identifying the specific genes involved in human differential aging has been difficult. Most human genetic studies of aging have focused on exceptional longevity which may be too far removed from the direct action of genes to be a reliable phenotype for genetic dissection. Additionally, much of the public health interest in aging is less in absolute longevity than in maintenance of normal function in old age. In the proposed project, we focus on quantitative differential aging in specific molecular pathways which should offer a more powerful approach to identify specific genes and their sequence variants that are involved in human variation in the aging process. In this project, we will identify a novel set of gene expression-based biomarkers using large-scale genome- wide transcriptional profiling of lymphocytes to identify quantitative phenotypes that are involved in differential aging. Such phenotypes have the great advantage of being directly proximal to gene action. An existing major human genetic resource (families from the San Antonio Family Heart Study) will be employed to examine the genetic basis of transcriptional aging in a cost-effective way. Extensive genome-wide genotypic and transcriptomic data from 1,240 Mexican Americans who are members of large extended pedigrees will be used. Analysis of existing cross-sectional transcriptional profiles from lymphocyte samples have revealed over 4,000 quantitative transcripts that correlate with age. For this project, we will perform follow-up transcriptional profiles on 1,000 of these individuals using lymphocytes obtained 15 years after the initial baseline examination. Using these novel mixed longitudinal transcriptional data, we will identify genes and their sequence variants that influence differential aging. The specific aims of this project are to: (1) develop a mixed longitudinal sample of genome-wide transcriptional profiles of lymphocytes from 1,000 Mexican Americans who are members of large extended kindreds; (2) localize quantitative trait loci influencing function/pathway-specific biological ages in order to detect genetic regulators of differential aging using linkage-based genome scanning; and (3) identify specific regulatory variants that interact with age to influence transcript levels in sixty novel cis-regulated aging-related genes. The proposed research should lead to the discovery of novel genes underlying variation in human biological aging. By focusing on novel-expression based phenotypes shown to be both age-related cis-regulated, we will maximize our probability for finding causal genetic variants influencing differential aging. Morbidity due to aging currently costs the United States billions of dollars annually and this economic burden is rapidly increasing. In this project, we will identify genes involved in human differential response to aging. A better understanding of the genetic underpinnings of molecular aging will provide novel approaches for the characterization, treatment and potential prevention of loss of vitality during aging and may lead to a significant reduction of this considerable public health burden.
描述(由申请人提供):从分子途径到器官系统的所有组织水平都观察到人类的年龄效应。虽然有大量证据表明遗传变异影响衰老发生的速度,但确定与人类差异衰老有关的特定基因一直很困难。大多数关于衰老的人类遗传研究都集中在异常长寿上,这可能与基因的直接作用相距甚远,无法作为遗传解剖的可靠表型。此外,公众对老龄化的兴趣更多的是在老年时维持正常功能,而不是绝对长寿。在拟议的项目中,我们将重点研究特定分子途径中的定量差异衰老,这将为识别人类衰老过程中涉及的特定基因及其序列变异提供更有力的方法。在这个项目中,我们将鉴定一组新的基于基因表达的生物标志物,使用大规模的全基因组淋巴细胞转录谱来鉴定与差异衰老有关的定量表型。这种表型具有直接接近基因作用的巨大优势。现有的主要人类遗传资源(来自圣安东尼奥家庭心脏研究的家庭)将被用于以经济有效的方式检查转录衰老的遗传基础。将使用来自1,240名墨西哥裔美国人的广泛全基因组基因型和转录组学数据,这些人是大型扩展谱系的成员。现有淋巴细胞样本的横断面转录谱分析揭示了超过4000个与年龄相关的定量转录本。在这个项目中,我们将使用初始基线检查后15年获得的淋巴细胞对1000名这些个体进行随访转录谱分析。利用这些新的混合纵向转录数据,我们将确定影响差异衰老的基因及其序列变异。该项目的具体目标是:(1)开发来自1000名墨西哥裔美国人的淋巴细胞全基因组转录谱的混合纵向样本,这些人都是大扩展家族的成员;(2)定位影响功能/途径特异性生物年龄的数量性状位点,利用基于连锁的基因组扫描检测差异衰老的遗传调控因子;(3)确定与年龄相互作用的特定调控变异,从而影响60个新型顺式调控的衰老相关基因的转录水平。拟议的研究应该导致发现新的基因在人类生物衰老的变化。通过关注与年龄相关的顺式调节的基于新表达的表型,我们将最大限度地提高发现影响差异衰老的因果遗传变异的可能性。目前,美国每年因老龄化引起的疾病花费数十亿美元,而且这一经济负担正在迅速增加。在这个项目中,我们将确定与人类对衰老的差异反应有关的基因。更好地了解分子衰老的遗传基础将为衰老过程中活力丧失的表征、治疗和潜在预防提供新方法,并可能显著减少这一相当大的公共卫生负担。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

SARAH A. WILLIAMS-BLANGERO其他文献

SARAH A. WILLIAMS-BLANGERO的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('SARAH A. WILLIAMS-BLANGERO', 18)}}的其他基金

Workforce Development Core
劳动力发展核心
  • 批准号:
    10749785
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
UTRGV Diversity Center for Genome Research
UTRGV 基因组研究多样性中心
  • 批准号:
    10749783
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10749784
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
Genetic Epidemiology of Chagas Disease Progression
恰加斯病进展的遗传流行病学
  • 批准号:
    8310010
  • 财政年份:
    2009
  • 资助金额:
    $ 55.67万
  • 项目类别:
Genetic Epidemiology of Chagas Disease Progression
恰加斯病进展的遗传流行病学
  • 批准号:
    7923210
  • 财政年份:
    2009
  • 资助金额:
    $ 55.67万
  • 项目类别:
Genetic Epidemiology of Chagas Disease Progression
恰加斯病进展的遗传流行病学
  • 批准号:
    8101324
  • 财政年份:
    2009
  • 资助金额:
    $ 55.67万
  • 项目类别:
Genetic Epidemiology of Chagas Disease Progression
恰加斯病进展的遗传流行病学
  • 批准号:
    7590884
  • 财政年份:
    2009
  • 资助金额:
    $ 55.67万
  • 项目类别:
Genetic Determinants of Human Transcriptional Aging
人类转录衰老的遗传决定因素
  • 批准号:
    7354276
  • 财政年份:
    2008
  • 资助金额:
    $ 55.67万
  • 项目类别:
Genetic Determinants of Human Transcriptional Aging
人类转录衰老的遗传决定因素
  • 批准号:
    7844851
  • 财政年份:
    2008
  • 资助金额:
    $ 55.67万
  • 项目类别:
Genetic Determinants of Human Transcriptional Aging
人类转录衰老的遗传决定因素
  • 批准号:
    8026871
  • 财政年份:
    2008
  • 资助金额:
    $ 55.67万
  • 项目类别:

相似国自然基金

靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
  • 批准号:
    JCZRQN202500010
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
  • 批准号:
    2025JJ70209
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    0 万元
  • 项目类别:
    面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
  • 批准号:
    2023JJ50274
  • 批准年份:
    2023
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    33 万元
  • 项目类别:
    地区科学基金项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
  • 批准号:
    n/a
  • 批准年份:
    2022
  • 资助金额:
    10.0 万元
  • 项目类别:
    省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
  • 批准号:
    81973577
  • 批准年份:
    2019
  • 资助金额:
    55.0 万元
  • 项目类别:
    面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
  • 批准号:
    81602908
  • 批准年份:
    2016
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
  • 批准号:
    81501928
  • 批准年份:
    2015
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

The Phenomenon of Stem Cell Aging according to Methylation Estimates of Age After Hematopoietic Stem Cell Transplantation
根据造血干细胞移植后甲基化年龄估算干细胞衰老现象
  • 批准号:
    23K07844
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Analysis of Age-dependent Functional Changes in Skeletal Muscle CB1 Receptors by an in Vitro Model of Aging-related Muscle Atrophy
通过衰老相关性肌肉萎缩的体外模型分析骨骼肌 CB1 受体的年龄依赖性功能变化
  • 批准号:
    22KJ2960
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Joint U.S.-Japan Measures for Aging and Dementia Derived from the Prevention of Age-Related and Noise-induced Hearing Loss
美日针对预防与年龄相关和噪声引起的听力损失而导致的老龄化和痴呆症联合措施
  • 批准号:
    23KK0156
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
    Fund for the Promotion of Joint International Research (International Collaborative Research)
The Effects of Muscle Fatigability on Gait Instability in Aging and Age-Related Falls Risk
肌肉疲劳对衰老步态不稳定性和年龄相关跌倒风险的影响
  • 批准号:
    10677409
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
Characterizing gut physiology by age, frailty, and sex: assessing the role of the aging gut in "inflamm-aging"
按年龄、虚弱和性别表征肠道生理学特征:评估衰老肠道在“炎症衰老”中的作用
  • 批准号:
    497927
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
Deciphering the role of osteopontin in the aging eye and age-related macular degeneration
破译骨桥蛋白在眼睛老化和年龄相关性黄斑变性中的作用
  • 批准号:
    10679287
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
Role of AGE/RAGEsignaling as a driver of pathological aging in the brain
AGE/RAGE信号传导作为大脑病理性衰老驱动因素的作用
  • 批准号:
    10836835
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
Elucidation of the protein kinase NLK-mediated aging mechanisms and treatment of age-related diseases
阐明蛋白激酶NLK介导的衰老机制及年龄相关疾病的治疗
  • 批准号:
    23K06378
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Underlying mechanisms of age-related changes in ingestive behaviors: From the perspective of the aging brain and deterioration of the gustatory system.
与年龄相关的摄入行为变化的潜在机制:从大脑老化和味觉系统退化的角度来看。
  • 批准号:
    23K10845
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Targeting Age-Activated Proinflammatory Chemokine Signaling by CCL2/11 to Enhance Skeletal Muscle Regeneration in Aging
通过 CCL2/11 靶向年龄激活的促炎趋化因子信号传导以增强衰老过程中的骨骼肌再生
  • 批准号:
    478877
  • 财政年份:
    2023
  • 资助金额:
    $ 55.67万
  • 项目类别:
    Operating Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了