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KAKEN_26460920seika.pdf
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Title |
Title |
エピゲノムの観点からの骨格筋加齢解析と心血管ホルモンによるミトコンドリアセラピー
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エピゲノム ノ カンテン カラ ノ コッカクキン カレイ カイセキ ト シンケツカン ホルモン ニ ヨル ミトコンドリア セラピー
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Epigenomu no kanten kara no kokkakukin karei kaiseki to shinketsukan horumon ni yoru mitokondoria serapi
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Elucidation of epigenetic alteration associated with aging in the muscle and the recovery by hormonal therapy targeting the mitochondria
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宮下, 和季
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Kana |
ミヤシタ, カズトシ
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Miyashita, Kazutoshi
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慶應義塾大学・医学部(信濃町)・専任講師
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Research team head
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科研費研究者番号 : 50378759
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伊藤, 裕
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イトウ, ヒロシ
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Ito, Hiroshi
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慶應義塾大学・医学部(信濃町)・教授
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Research team member
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科研費研究者番号 : 40252457
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田蒔, 昌憲
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タマキ, マサノリ
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Tamaki, Masanori
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慶應義塾大学・医学部(信濃町)・助教
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Research team member
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科研費研究者番号 : 90528902
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三石, 正憲
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ミツイシ, マサノリ
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Mitsuishi, Masanori
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慶應義塾大学・医学部(信濃町)・助教
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Research team member
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科研費研究者番号 : 50468485
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2017
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科学研究費補助金研究成果報告書
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2016
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Abstract |
慢性腎臓病(CKD)では, 身体能力の低下が腎機能を悪化させるリスクとなり, さらには, 心血管病発症率を大きく上昇させる。消化管ホルモンであるグレリンは, ラット骨格筋ミトコンドリアに作用して酸素消費を増やすと報告された。そこでグレリンがCKDに伴うミトコンドリア不全を改善する可能性を考え, 5/6腎摘CKDモデルマウスにグレリンを週3回腹腔内投与し, 1ヶ月後に骨格筋ミトコンドリアと身体能力を検討した。グレリンは5/6腎摘マウスの筋力と持久力を増加させ, 5/6腎摘により低下した身体能力を効率よく改善した。グレリン投与マウスの下腿筋では, ミトコンドリアの活性化に加えて筋肉量の増加を認めた。
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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研究種目 : 基盤研究(C)(一般)
研究期間 : 2014~2016
課題番号 : 26460920
研究分野 : 内分泌学, 代謝学, 抗加齢医学
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