2021 Fiscal Year Final Research Report
Exploring Mitochondrial epigenomic modifications in aging
| Project/Area Number |
20K22890
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0902:General internal medicine and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Keywords | 老化 / 加齢 / ミトコンドリア / エピゲノム |
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| Outline of Final Research Achievements |
Mitochondrial DNA (mtDNA), the unique genome of mitochondria, is a key issue in aging, as its mutation is strongly correlated with age-related decline in individual function, and elucidation of the molecular mechanism of mtDNA mutation is important for the control of aging. Among the mtDNA transcription-replication related proteins, an increase in mitochondrial transcription elongation factor (TEFM) was observed in organs of super-aged mice (24-month-old).Met-tRNA and other tRNAs were significantly decreased in all organs (liver, kidney and heart). It was suggested that age-related disruption of the mtDNA transcription-translation machinery may inhibit the supply of sufficient modified tRNA and contribute to the age-related decline in mitochondrial function.
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| Free Research Field |
加齢医学
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| Academic Significance and Societal Importance of the Research Achievements |
ミトコンドリアは独自のゲノムであるミトコンドリアDNA （mtDNA）を有し、呼吸鎖複合体の構造遺伝子およびそれらの翻訳に必要なtRNA遺伝子やrRNA遺伝子をコードする。mtDNA異常は呼吸鎖複合体の遺伝子発現を障害し、様々な疾患の発症につながる。特に老化においては、mtDNAの変異が加齢に伴う個体機能低下と強く相関しており、老化制御に向けてmtDNA変異の分子機構の解明が重要である。本研究では超加齢マウスにおいてミトコンドリア伸長因子であるTEFMが増加し、ミトコンドリアtRNAが減少していることを明らかにし、加齢によるミトコンドリア機能低下の一因が転写翻訳機能低下である可能性を示した。
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