A molecular mechanism of aging through epigenome and muscle regeneration

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K13228
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: Keio University
• Principal Investigator: Hayano Motoshi 慶應義塾大学, 医学部(信濃町), 特任講師 (30593644)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 老化 / エピゲノム / DNA損傷 / 筋肉 / サルコペニア

Outline of Final Research Achievements

ICE (Induced changes in epigenome) mice is a novel mouse model in which aging related phenotypes and the changes in epigenome are induced by DNA damage through I-PpoI endonuclease. By induction of DNA damage for three weeks at 4 to 6 months age in mice, muscle mass and muscle functions are declined at 10 months post-treatment. Transcriptome analysis with RNA-seq showed ribosomal genes (RPS28 and RPS 24), OXPHOS genes (ATP5k, Ndufa8, COX8) and myosin-related genes (Myh7, Myh9) are altered at 10 month after induction of aging along with changes in H3K4me1 and H4K20me1 at those genes in ICE mice. Those data indicate that LSD1 and SETD8 invloved in regulation of aging and muscle function during aging.

Free Research Field

老化

Academic Significance and Societal Importance of the Research Achievements

老化に伴ってDNA損傷の蓄積やエピゲノム変化が報告されており、DNA損傷による老化や老化関連疾患誘導の分子機序が着目されてきた。その中で、DNA損傷によってゲノム変異を伴わないエピゲノム変化による老化は、生後生じる老化誘導の分子機序をあきらかにするだけでなく、老化の可逆性を証明することが可能となる。本研究によって、DNA損傷は特異的なエピゲノム変化と遺伝子発現を引き起こすことで、老化速度を変化させることをあきらかにした。今後、代謝やタンパク質合成を含めた制御を介してエピゲノムを標的としたサルコペニア創薬の基盤となる。