Elucidation of epigenetic alteration associated with aging in the muscle and the recovery by hormonal therapy targeting the mitochondria

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460920
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Keio University
• Principal Investigator: Miyashita Kazutoshi 慶應義塾大学, 医学部(信濃町), 専任講師 (50378759)
• 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• 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

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).

Free Research Field

内分泌学、代謝学、抗加齢医学