Regulation of aging in mammals : Difference between the effects of calorie restriction and suppression of the GH-IGF-1 axis
Regulation of aging in mammals : Difference between the effects of calorie restriction and suppression of the GH-IGF-1 axis
批准号:
15390128
负责人:
SHIMOAKAWA Isao
金额:
$4.93万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2003
资助国家:
日本
项目状态:
已结题
起止时间:
2003 至 2005
中文摘要
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英文摘要
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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Handbook for Models of Human Aging (Chapter 31 A transgenic mini rat strain as a tool for studying aging and calorie restriction)
人类衰老模型手册(第31章转基因迷你大鼠品系作为研究衰老和热量限制的工具)
DOI:
--
发表时间:
2006
期刊:
影响因子:
--
作者:
[Shimokawa I., Higami Y 他, 林 洋子 他, Yamaza H, Tanaka K, 樋上 賀一, 嘉陽 毅, Shimokawa I., Shimokawa I., 下川 功, Shimokawa I, Shimokawa I, Shimokawa I (Conn M編集)]
通讯作者:
Shimokawa I (Conn M編集)
DOI:
--
发表时间:
2006
期刊:
J Gerontology (in press)
影响因子:
--
作者:
[Cao, X., Tsukamoto, T., Nozaki, K., Mizoshita, T., Ogasawara, N., Tanaka, H., Takenaka, Y., Kaminishi, M., Tatematsu, M., Higami Y, Komatsu T]
通讯作者:
Komatsu T
Calorie restriction/Healthy aging (in Japanese)
热量限制/健康老龄化(日语)
DOI:
--
发表时间:
2006
期刊:
Gerontology New Horizon 18
影响因子:
--
作者:
[Komatsu T, Chiba T, Yamaza H, To K, Toyama H, Higami Y, Shimokawa I., Shimokawa I.]
通讯作者:
Shimokawa I.
Laboratory findings of caloric restriction in rodents and primates
啮齿动物和灵长类动物热量限制的实验室结果
DOI:
--
发表时间:
2005
期刊:
Adv Clin Chem 39
影响因子:
--
作者:
[Mizoshita, T., Tsukamoto, T., Nakanishi, H., Inada, K., Ogasawara, N., Joh., T., Itoh, M., Yamamura, Y., Tatematsu, M., Higami Y]
通讯作者:
Higami Y
DOI:
10.1016/j.mad.2004.11.007
发表时间:
2005-05-01
期刊:
MECHANISMS OF AGEING AND DEVELOPMENT
影响因子:
5.3
作者:
[Tsuchiya, T, Higami, Y, Shimokawa, I]
通讯作者:
Shimokawa, I
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