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DNA methylation markers of Multimorbidity in Aging Humans and Mice

衰老人类和小鼠多种疾病的 DNA 甲基化标记

基本信息

批准号：
10551502
负责人：
Shabnam Salimi
金额：
$ 12.14万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10551502
关键词：
20 year old Affect Age Aging Animal Model Baltimore Biological Markers Blood Blood Cells CRISPR/Cas technology Caregivers Cell Line Cells Cessation of life Chronic Disease Chronology Clinical Complex DNA DNA Methylation DNA analysis Data Development Effectiveness of Interventions Elderly Environmental Risk Factor Epigenetic Process Ethics Female Functional disorder Future Gene Expression Genotype Goals Gold Health Health Status Histopathology Hospitalization Human Iatrogenesis Individual Intervention Lesion Light Link Logistics Longitudinal Studies Measures Metformin Methylation Microscopic Mus Natural Immunity Organ Outcome Pathology Pathway Analysis Pathway interactions Patient Self-Report Patients Phenotype Polypharmacy Population Prevention Public Health Quality of life Research Personnel Retirement Risk Sampling Serum Site Societies Surveys Syndrome System Testing Time Tissues Werner Syndrome Whole Blood Woman Women&apos s Health Work adverse outcome age related aged base bisulfite sequencing case control cell type clinical diagnosis clinical examination clinical practice clinical predictors cohort cost disability effectiveness testing experience healthspan high risk human DNA indexing interest longitudinal human study male men methylation biomarker monocyte mortality mouse model multiple chronic conditions neglect premature sex success tool transcriptome sequencing transcriptomics whole genome

项目摘要

Multimorbidity (MM), conventionally defined as two or more chronic diseases, is a public health problem in older adults. MM patients are at high risk of iatrogenesis from polypharmacy, disability, and premature death, with challenges to caregivers and cost to society. The study of the pathophysiology of MM based on single biomarkers or pathways has had limited success. Moreover, there are no comprehensive biomarkers developed to evaluate and predict MM. Previous experience and preliminary data corroborate the hypothesis of the existence of potential DNA methylation (DNAm) biomarkers that are associated with MM at the population level. Additionally, the study of mechanisms of MM at the tissue level in humans have been limited due to ethical and logistical complications. Neglected yet unarguably pivotal, identifying DNAm markers associated with MM mouse models is of paramount importance to develop our capabilities to predict MM and shed more light on its underlying mechanisms. The overarching goal of this proposal is to identify DNAm markers of MM in human populations and mouse models to develop a set of comprehensive tools for the identification of at-risk individuals. The resulting markers will be applicable to both male and female individuals. Using four population cohorts, I will test the use of DNAm markers to predict who is likely develop MM. I will measure how cell specific DNAm and gene expression (RNA-seq) are related and different between individuals who are free of MM at baseline and developed MM and those who remained free of MM. I will use an animal model of MM using histopathology studies of organs to define mm and measure DNAm and cognate transcriptomics (RNA-seq). The results of this study can be used to better identify and understand the shared mechanism(s) that causes MM. Collectively, identifying “DNA methylation markers of multimorbidity in aging humans and mice” should allow geriatricians to predict multimorbidity in older adults and help researchers to further understand the mechanisms underlying multimorbidity. The results of this project, in the future, can be applied to test the effectiveness of interventions such as metformin that target these mechanisms for prevention and treatment of MM.

多病（MM），通常定义为两种或两种以上的慢性疾病，是一个公共卫生问题