Identify FoxO1 and FoxO3a target genes that relate to anti-neoplastic effect and the anti-aging effect of calorie restriction

• Project/Area Number: 25860297
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Nagasaki University
• Principal Investigator: KOMATSU Toshimitsu 長崎大学, 医歯薬学総合研究科(医学系), 技術職員 (70380962)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: カロリー制限 / 抗老化 / 抗腫瘍効果 / FoxO / ミトコンドリア / マイクロアレイ解析 / 肝臓 / 寿命延長

Outline of Final Research Achievements

Transcription factor, FoxO1 and FoxO3a, may regulate anti-neoplastic effect and lifespan extension effect of calorie restriction (CR), respectively. However, most of target genes of FoxO1 and FoxO3a are common, and the mechanisms that the specific target genes are regulated by each FoxOs are unknown. In this study, we identified the anti-neoplastic effect related genes and the lifespan extension effect related genes using microarray analysis that were regulated by FoxO1 and FoxO3a, respectively. Especially, FoxO3a knock down affected to the expression of mitochondria related genes. Actually, isolated mitochondria from FoxO3a KO mice under CR showed abnormal activity compared with the mitochondria from the wild type-CR mice. These results suggest that the regulation of mitochondria function by FoxO3a, not FoxO1, might be important for CR induced lifespan extension effect.