Genome-wide methylation profiles to develop a predictive model for the human biological age

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04151
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Iwate Medical University
• Principal Investigator: Hitomi Jiro 岩手医科大学, 医学部, 教授 (00218728)
• Co-Investigator(Kenkyū-buntansha): 三上 貴浩 岩手医科大学, 医学部, 助教 (90804419) ; 村嶋 亜紀 岩手医科大学, 医学部, 助教 (50637105) ; 丹野 高三 岩手医科大学, 医学部, 准教授 (20327026) ; 寺山 靖夫 岩手医科大学, 医学部, 教授 (70146596)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: エピゲノム / メチローム / 生物学的年齢 / 末梢血単核球

Outline of Final Research Achievements

WWe have established the idea that common DNA methylation (DNAm) variations (CDMV) are more likely to be associated with environmental exposures or biomedical traits than rare DNAm variations(Hachiya et al., 2017). Based on this CDMV strategy, we have developed methyl- capture sequencing method with newly designed catalogues of inter-individually variable CpG sites as targets for DNAm profiling, whose efficacy were estimated significantly higher than that of the most frequently used EWAS methods. Utilizing this novel method, we obtained genome-wide CDMV profiles of peripheral blood mononuclear cells from 529 individuals recruited as part of the Tohoku Medical Megabank Project. Participants were divided into two groups, G1(384, including 113 males), G2 (145, including 75 males) aged 20 to 86 years. We attempted to establish the calculation method to identify the DNAm biomarkers of cellular biological age as a predicting model for the human biological age.

Free Research Field

解剖学

Academic Significance and Societal Importance of the Research Achievements

本研究は老化のメカニズムを解明することを目的としている。老化はDNAのメチル化が深く関わっていると考えられており、これまでの研究では「細胞分化に関与しているゲノム領域が加齢のDNAマーカーになりやすい」との仮説に基づき、細胞分化に係るDNAのCpG領域を中心にDNAのメチル化解析が進められてきた。しかし、本研究では個人間バリエーションの高い領域に注目し、解析を行なったが、個人間のバリエーションのバラツキは老年層でさらに拡大する傾向を示した。個人間バリエーションの高い領域に注目することで、個人間の「年の取り易さ」の差異を考慮した精度の高い「細胞加齢尺度」の開発できる可能性が高い。