Elucidation of the mechanisms of epidermal aging
| Project/Area Number |
19K16607
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | The University of Tokyo (2021)
Tokyo Medical and Dental University (2019-2020) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 皮膚 / 幹細胞 / 老化 / 毛包 / ストレス |
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| Outline of Research at the Start |
多くの組織において固有の幹細胞が機能細胞を供給することにより恒常性が維持され、何らかの原因による恒常性維持システムの破綻は個体の死へ繋がる。その過程で各組織は老化形質を獲得するが、老化システムや実体はほとんど理解されていない。申請者らは最近、加齢毛包では毛包幹細胞や色素幹細胞は自己複製を行わず異所性に分化細胞へと運命転換することで脱毛や白髪に至ることを明らかにし、「幹細胞の制御機構の破綻」が老化形質獲得の一端であることを示した。本研究では、マウス毛包・皮膚をモデルとして老化形質獲得の要因とそのメカニズムの理解を目的とする。
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| Outline of Final Research Achievements |
In order to understand the physiological aging mechanism of the epidermis, we analyzed changes in skin function and stem cell behavior during aging using the mouse epidermis as a model.
Environmental factors that cause DNA damage, such as radiation and UVB, lead to functional decline similar to that of aged skin.Fate analysis revealed that DNA damage of epidermal stem cell leads to differentiated and then withdraw from the basal layer of the epidermis during homeostasis in young mice.Similar results were demonstrated in three-dimensional culture using human epidermal cells.
These results indicating that tissue regeneration by withdrawal of DNA damaged stem cells from the basal layer is a conserved maintenance mechanism of epidermal stem cell pool throughout the species.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、加齢性の皮膚機能低下において表皮幹細胞の加齢変化、すなわち幹細胞老化が組織における老化形質出現の中心的な役割を果たすこと、また、幹細胞においてDNA障害を引き起こす種々の環境因子が組織老化促進因子としての重大なリスクファクターとなりうることを示した。本成果に基づく幹細胞老化の抑制を作用点とした、超高齢化社会における抗老化技術の開発へと繋がるものと期待できる。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Obesity accelerates hair thinning by stem cell-centric converging mechanisms2021
Author(s)
Morinaga H, Mohri Y, Grachtchouk M, Asakawa K, Matsumura H, Oshima M, Takayama N, Kato T, Nishimori Y, Sorimachi Y,?Takubo K, Suganami T, Iwama A, Iwakura Y, Dlugosz AA, Nishimura EK.
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Journal Title
Nature
Volume: 595
Issue: 7866
Pages: 266-271
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Stem cell competition orchestrates skin homeostasis and ageing2019
Author(s)
Liu N, Matsumura H, Kato T, Ichinose S, Takada A, Namiki T, Asakawa K, Morinaga H, Mohri Y, De Arcangelis A, Geroges-Labouesse E, Nanba D, Nishimura EK
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Journal Title
Nature
Volume: 568(7752)
Issue: 7752
Pages: 344-350
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
