Discovery of novel progeroid syndrome loci and contribution to normative aging
| Project/Area Number |
17H04037
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Chiba University |
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Principal Investigator |
OSHIMA JYUNKO 千葉大学, 大学院医学研究院, 特任教授 (80792275)
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| Co-Investigator(Kenkyū-buntansha) |
田中 知明 千葉大学, 大学院医学研究院, 教授 (50447299)
横手 幸太郎 千葉大学, 大学院医学研究院, 教授 (20312944)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | 遺伝学 / ゲノム / 老化 / 内科 / 早老症 |
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| Outline of Final Research Achievements |
From results of this study, in the molecular pathophysiology of progeria syndrome based on DNA damage, cells with its causative mutations can be considered by accounting for the involvement of mitochondrial interactions via caloric restriction as well as rapamycin (mTOR pathway inhibitor). It was suggested that autophagy level may be reduced to near normal level with long-term use, and thereby the DNA damage accumulation may be reduced and subsequently cell proliferation rate may be restored. Taken together, it is fully assumed that the p38MAPK inhibitor would be useful as one of the drug discovery targets, and it was shown that the inhibitory effect can be expected to reduce the accumulation of DNA damage and prolong the cell life.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究のように国際コンソーシアムを用いて早老遺伝子候補を発見することでその分子基盤が明らかにされ、更に遺伝子が早老表現型を起こすメカニズムが分子レベルで解明し、動物モデルで実証していくことは、有効な治療薬のないこの難病と正常の老化制御の接点で機能する遺伝子や分子群のシグナル研究分野において非常に重要である。また、早老遺伝子が、どの程度加齢疾患の進行や寿命に関連するかを人口学的に調査し、老化の過程への関与を明らかにするような社会疫学的/遺伝学的融合研究の推進も重要である。これらの研究は、早老症の有効な治療法、加齢関連疾患の治療、一般高齢者の健康維持の開発、健康長寿社会の実現に大いに貢献できる。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures2018
Author(s)
6.Sargolzaeiaval F, Zhang J, Schleit J, Lessel D, Kubisch C, Precioso DR, Sillence D, Hisama FM, Dorschner M, Martin GM, Oshima J.
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Journal Title
Molecular Genetics & Genomic Medicine
Volume: 6
Issue: 6
Pages: 1148-1156
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Biallelic WRN Mutations in Newly Identified Japanese Werner Syndrome Patients2018
Author(s)
Maezawa Y, Kato H, Takemoto M, Watanabe A, Koshizaka M, Ishikawa T, Sargolzaeiaval F, Kuzuya M, Wakabayashi H, Kusaka T, Yokote K, Oshima J
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Journal Title
Mol Syndromol
Volume: 9
Issue: 4
Pages: 214-218
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies.2018
Author(s)
Horvath S, Oshima J, Martin GM, Lu AT, Quach A, Cohen H, Felton S, Matsuyama M, Lowe D, Kabacik S, Wilson JG, Reiner AP, Maierhofer A, Flunkert J, Aviv A, Hou L, Baccarelli AA, Li Y, Stewart JD, Whitsel EA, Ferrucci L, Matsuyama S, Raj K.
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Journal Title
Aging (Albany NY)
Volume: 10
Issue: 7
Pages: 1758-1775
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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