Epitranscriptomics of the aging lung

衰老肺的表观转录组学

基本信息

批准号：
10322154
负责人：
DAWN L DEMEO
金额：
$ 26.85万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10322154
关键词：
Address Adenosine Age Aging Anatomy Biological Markers Biology Biology of Aging Cardiac Cardiac Myocytes Complex DNA Data Dependence Disease Environmental Exposure Epigenetic Process Evaluation Gene Expression Genes Genetic Genetic Variation Genomics Health Human Genome Individual Investigation Life Life Cycle Stages Lung Mediator of activation protein Messenger RNA Methylation Methyltransferase Modeling Modification Molecular Molecular Profiling Normal Range Pathway interactions Physiological Publishing RNA RNA Splicing RNA methylation Race Reader Research Role Sex Differences Specimen Spirometry Strategic vision Structure of parenchyma of lung System Time Transcript Untranslated RNA Variant age difference age related clinical phenotype epitranscriptome epitranscriptomics gene function gene regulatory network genetic association genome sequencing genome-wide heart function insight lung health methylome normal aging pulmonary function pulmonary function decline resilience respiratory respiratory health sex transcriptome sequencing whole genome

项目摘要

ABSTRACT Normal aging of the pulmonary system associates with a multitude of physiologic, anatomic and molecular changes in the lung. Epigenetic marks, non-sequence based variations in the human genome, have been identified as important molecular hallmark of normal aging, with investigations mainly focused on DNA, not RNA, methylation. Epitranscriptomics refers to studies of modifications of RNA. N6-methyl-adenosine (m6A) is the most studied of these RNA modifications, but aging-related global RNA methylation in lung tissue has not been explored. We hypothesize that differential RNA methylation in lung tissue may represent a new research direction for advancing understanding of normal lung biology and genomics changes with aging. Given the growing evidence that normal aging has a cumulative molecular impact, considering age-related changes to the epitranscriptome may advance insights into age-related resilience in the lung. We will investigate global RNA methylation through the following Specific Aims : 1) Quantification of global N6-methyl-adenosine in lung tissue from 400 individuals with normal spirometry from the Lung Tissue Research Consortium, exploring variability of RNA methylation with age, with additional consideration of sex and race associated variability; 2) Identification of genetic variation that associates with RNA methylation; 3)Evaluation of RNA methylation as a predictor of gene expression and a contributor to gene regulatory network signatures in lung tissue. There are no published studies of RNA methylation and aging in the normal lung. This project will address whether RNA methylation captures normal aging in the lung and will support more in-depth evaluations of the epitranscriptome as a marker of lung health. This proposal is responsive to PA-19-049 (New Research Directions to Advance the NHBLI Strategic Vision Normal Biology) by modeling aging associated non-sequence variation of RNA in lung tissue from individuals with normal lung function.

抽象的肺系统的正常衰老与多种生理，解剖和分子相关联肺的变化。表观遗传标记，人类基因组中的非序列变异已是被认为是正常衰老的重要分子标志，研究主要集中于DNA，而不是RNA，甲基化。表参见分析组是指RNA修饰的研究。 N6-甲基 - 腺苷（M6A）是最多的研究了这些RNA修饰，但是肺组织中与衰老相关的全局RNA甲基化尚未探索。我们假设肺组织中的差异RNA甲基化可能代表一个新的研究方向为了促进对正常肺生物学和基因组学的理解，随着衰老的变化。考虑到增长正常衰老具有累积分子影响的证据，考虑到年龄相关的变化表面参考组可能会提高人们对肺部与年龄相关的弹性的见解。我们将研究全球RNA 通过以下特定目的甲基化：1）定量肺组织中全球N6-甲基腺苷从肺组织研究联盟的400名患有正常肺活量法的个体，探索可变性随着年龄的增长，RNA甲基化，并考虑性别和种族相关的变异性； 2）识别与RNA甲基化相关的遗传变异； 3）评估RNA甲基化作为预测因子基因表达和肺组织中基因调节网络特征的贡献者。没有出版正常肺中RNA甲基化和衰老的研究。该项目将解决RNA甲基化是否在肺中捕获正常衰老，并将支持对表演组的更深入的评估作为标记肺部健康。该提案对PA-19-049（推进NHBLI的新研究指示）有回应战略视觉正常生物学）通过对肺组织中RNA相关的非序列变化进行建模。来自具有正常肺功能的个体。