| Project/Area Number |
15390128
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Nagasaki University Graduate School of Biomedical Sciences |
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Principal Investigator |
SHIMOAKAWA Isao Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (70187475)
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| Co-Investigator(Kenkyū-buntansha) |
HIGAMI Yoshikazu Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (90253640)
CHIBA Takuya Nagasaki University, Graduate School of Biomedical Sciences, Assistant Professor, 大学院・医歯薬学総合研究科, 助手 (40336152)
山座 治義 長崎大学, 大学院・医歯薬学総合研究科, 助手 (30336151)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2004: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | Aging / Longevity / Calorie-restriction / Insulin / Growth hormone / Insulin-like growth factor / Stress response / Energy metabolism |
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| Research Abstract |
1.Insulin signaling : The insulin signaling was analyzed in liver and skeletal muscle in CR and GH-IGF-1-suppressed transgenic (Tg) rats. The results suggested that CR not only sensitized the insulin action for glucose metabolism but also activated insulin-independent pathways. These mechanisms induced by CR could result from the suppressed GH-IGF-1 axis (Yamaza H et al., Exp Gerontol 2004 ; Hayashi H et al. Biomedical Gerontol 2005). We investigated a potential role for the adiponectin-AMP-activated protein kinase (AMPK) pathway in insulin-independent mechanisms. However, unexpectedly, CR suppressed the activity of AMPK and also the suppressed GH-IGF-1 axis did not affect the AMPK pathway.
2.Stress response : We analyzed the inflammatory stress response in CR rats using the DNA array method. The results confirmed the stress-resistance in CR rats. The DNA array analysis in liver suggested that the protective effect by CR emerges from constitutively, rather than NF-kappa B-inductively, expressed gene products (Tsuchiya T et al., Mech Ageing Develop 2005). GH-IGF-1-suppressed rats exhibited greatly enhanced stress response. This effect could be partly due to attenuation of the NF-kappa B-induced proinflammatory response. At present, we are investigating redox-sensitive transcription factors and signaling pathways other than the NF-kappa B pathway.
3.Oxidative stress in mitochondria : Analyses including glutathione and glutathione disulfide indicated that severe suppression of GH-IGF-1 axis induced oxidative stresses, increased neoplastic diseases, and shorten lifespan in rats, although moderate suppression of GH-IGF-1 axis increased lifespan.
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