IGF-1 signaling and aging

被引:49
作者
Holzenberger, M [1 ]
Kappeler, L [1 ]
De Magalhaes, C [1 ]
机构
[1] Hop St Antoine, INSERM, U515, F-75571 Paris 12, France
关键词
insulin-like growth factors; growth hormone; pituitary gland; hypothalamus; animal models; mouse;
D O I
10.1016/j.exger.2004.08.017
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
We briefly compare calorie restriction, GHRH-R and Pit-1 mutants with knockout phenotypes of GH receptor, IGF-1 receptor and p66Shc, to make some general conclusions. Growth, fertility and longevity phenotypes may dissociate in some of these mutants, and we try to interpret this. Follows a short discussion on the importance of genetic background for aging studies in mice. We then evoke studies in C elegans showing that lifespan may be regulated in a non-cell-autonomous fashion, and that the nervous system could play a central role therein. Recent findings on DILP-2 regulation in Drosophila transpose this hypothesis of endocrine lifespan regulation to insects. Work in mice shows that inactivation of the insulin receptor specifically in the adipose tissue is sufficient to increase the mouse lifespan. In summary, exciting findings obtained in very different model organisms are rapidly converging and suggest that animal lifespan may be subject to endocrine regulation. Interestingly, the hypothalamus centralizes many age related hormonal regulations and at the same time participates in the integration of numerous nutritional signals, such that one could ask whether the hypothalamus may be at the crossroads of metabolic and endocrine lifespan regulation. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:1761 / 1764
页数:4
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