Elucidation of epigenetic alteration associated with aging in the muscle and the recovery by hormonal therapy targeting the mitochondria
| Project/Area Number |
26460920
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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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| Research Field |
General internal medicine(including psychosomatic medicine)
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| Research Institution | Keio University |
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Principal Investigator |
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| Research Collaborator |
ITOH Hiroshi 慶應義塾大学, 医学部(信濃町), 教授 (40252457)
TAMAKI Masanori 慶應義塾大学, 医学部(信濃町), 助教 (90528902)
MITSUISHI Masanori 慶應義塾大学, 医学部(信濃町), 助教 (50468485)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 身体能力 / サルコペニア / ミトコンドリア / 骨格筋 / グレリン / 内分泌学 / 抗加齢医学 / エピゲノム |
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| Outline of Final Research Achievements |
Chronic kidney disease (CKD) is a representative age-asociaed disease which impairs physical performance. We found that decrease in muscle mitochondria rather than muscle mass was a major cause of physical decline in 5/6 nephrectomized (5/6Nx) CKD model mice (Kidney Int 85:1258, 2014). Because ghrelin has both muscular hypertrophy and mitochondrial oxidation effect, we examined the usefulness of ghrelin for a recovery of physical decline in 5/6Nx mice, focused on the epigenetic modification of PGC-1alpha. 5/6Nx mice were intraperitoneally administered acylated ghrelin for a month. The methylation level of the cytosine residue at 260 base pairs upstream (C-260) of initiation point of PGC-1alpha gene, which was demonstrated to decrease the gene expression, was evaluated by methylation specific PCR and bisulfite sequencing. Ghrelin treatment efficiently improved both muscle mass and mitochondria, associated with the epigenetic modification of PGC-1alpha (Endocrinology 156:3638, 2015).
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Treatment of sarcopenia and glucose intolerance through mitochondrial activation by 5-aminolevulinic acid.2017
Author(s)
Fujii C, Miyashita K, Mitsuishi M, Sato M, Fujii K, Inoue H, Hagiwara A, Endo S, Uto A, Ryuzaki M, Nakajima M, Tanaka T, Tamaki M, Muraki A, Kawai T, Itoh H.
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Journal Title
Scientific Reports
Volume: -
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Improvement of Physical Decline Through Combined Effects of Muscle Enhancement and Mitochondrial Activation by a Gastric Hormone Ghrelin in Male 5/6Nx CKD Model Mice.2015
Author(s)
Tamaki M, Miyashita K, Wakino S, Hagiwara A, Inoue H, Fujii K, Fujii C, Mitsuishi M, Muraki A, Hayashi K, Doi T, Itoh H.
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Journal Title
Endocrinology
Volume: 156
Pages: 3638-3648
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] 慢性腎臓病におけるサルコペニアと骨格筋ミトコンドリアの活性化2016
Author(s)
宮下 和季, 藤井 千華子, 田蒔 昌憲, 萩原 あいか, 井上 博之, 藤井 健太郎, 遠藤 翔, 宇都 飛鳥, 佐藤 正明, 脇野 修, 伊藤 裕
Organizer
第1回 CKD-MBD交流会
Place of Presentation
渋谷エクセルホテル東急 （東京都渋谷区）
Year and Date
2016-06-24
Related Report
Invited
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