Regulatory mechanisms for senescence marker protein 30 expression

• Project/Area Number: 23500838
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: The University of Tokyo
• Principal Investigator: ARAI Hideaki 東京大学, 総合文化研究科, 助教 (60313160)
• Co-Investigator(Renkei-kenkyūsha): MARUYAMA Naoki 東京都健康長寿医療センター研究所, 参事研究員(副所長) (00115940)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 老化 / 加齢 / アンチエイジング / 遺伝子 / シグナル伝達 / FOXO / ストレス耐性 / サーチュイン / SMP30 / 長寿

Research Abstract

Senescence marker protein 30 (SMP30) was identified as a marker protein which shows substantial decrease in ageing rat liver. The molecular mechanisms regulating SMP30 expression is unclear. Elucidation of this regulatory mechanisms is crucial for development of countermeasures against age-related decline of physical fitness and age-associated diseases. Ageing is a highly regulated process with evolutionally conserved signal transduction mechanisms, among which insulin-insulin like growth factor signaling (IIS) is predominantly important. In this study, I found that SMP30 expression in human HepG2 cells was regulated by IIS. Detailed analysis of human SMP30 gene indicated that SMP30 is regulated by Forkhead box transcription factor class O (FoxO), an ortholog of worm longevity gene daf-16. However, direct demonstration of FoxO involvement was hardly feasible because of the extremely low level of SMP30 expression in HepG2, probably reflecting lack of cofactor(s) for FoxO regulation.