2005 Fiscal Year Final Research Report Summary
Regulation of aging in mammals : Difference between the effects of calorie restriction and suppression of the GH-IGF-1 axis
| 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)
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| Project Period (FY) |
2003 – 2005
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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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