2023 Fiscal Year Final Research Report
Transcriptomic analyses of mouse cardiac myocytes and cardiac non-myocyte cells: postmitotic vs. proliferative cells
| Project/Area Number |
21K11605
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平崎 正孝 埼玉医科大学, 医学部, 講師 (10522154)
柿沼 由彦 日本医科大学, 大学院医学研究科, 大学院教授 (40233944)
大畠 久幸 日本医科大学, 医学部, 講師 (80256924)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 老化 / 心筋 / 非心筋 / 分裂終了細胞 / トランスクリプトーム解析 / ミトコンドリア / 核小体低分子RNA / snoRNA |
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| Outline of Final Research Achievements |
Adult heart mostly contains long-lived postmitotic cardiomyocytes and non-cardiomyocytes that have proliferative potential. Here, we isolated cardiomyocytes and non-cardiomyocytes from young and aged mouse heart, and performed transcriptome analyses to understand the differences of gene expression in postmitotic and proliferative cells. Gene ontology analyses revealed that genes associated with inflammatory response were upregulated in aged cardiac myocytes, whereas genes including two ATP synthases in mitochondrial respiratory were significantly downregulated. We also found that the expression levels of some small nucleolar RNAs (snoRNAs) are decreased cardiomyocytes with aging. snoRNAs are deeply involved in RNA modification such as pseudouridylation stabilizing ribosomal RNA and mRNA splicing. Therefore, the age-related reduction in snoRNA expression may lead to the destabilization of rRNA, splicing dysfunction, and ultimately a decrease in protein synthesis capacity.
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| Free Research Field |
老化生理学
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| Academic Significance and Societal Importance of the Research Achievements |
老化研究は老化に伴う組織の機能低下に加えて多くの疾患の診断や治療を根底から変える可能性を秘めており、老化の根本的なメカニズム解明は高齢化の進む現代において急務である。多くの多細胞生物において老化とは分裂細胞の分裂限界として現れる現象と、非分裂性細胞の生存限界として現れる現象との重なり合いの結果である。本研究の成果により将来的には、当該老化マーカーのカイネティクスを元にした個体老化レベルの多面的評価法の確立が期待される。また既に蓄積したマーカー分子の軽減、消去法を模索することによる老化表現型の緩和や高齢期における心機能低下の治療への応用も期待される。
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