Cohen Dena E, Supinski Andrea M, Bonkowski Michael S, Donmez Gizem, Guarente Leonard P
Paul F. Glenn Laboratory, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Genes Dev. 2009 Dec 15;23(24):2812-7. doi: 10.1101/gad.1839209.
Mammalian life span can be extended by both calorie restriction (CR) and mutations that diminish somatotropic signaling. Sirt1 is a mediator of many effects of CR in mammals, but any role in controlling somatotropic signaling has not been shown. Since the somatotropic axis is controlled by the brain, we created mice lacking Sirt1 specifically in the brain and examined the impacts of this manipulation on somatotropic signaling and the CR response. These mutant mice displayed defects in somatotropic signaling when fed ad libitum, and defects in the endocrine and behavioral responses to CR. We conclude that Sirt1 in the brain is a link between somatotropic signaling and CR in mammals.
卡路里限制(CR)和减少生长激素信号传导的突变都可以延长哺乳动物的寿命。Sirt1是CR在哺乳动物中多种效应的介导因子,但尚未发现其在控制生长激素信号传导方面有任何作用。由于生长激素轴由大脑控制,我们构建了大脑中特异性缺乏Sirt1的小鼠,并研究了这种操作对生长激素信号传导和CR反应的影响。这些突变小鼠在随意进食时表现出生长激素信号传导缺陷,以及对CR的内分泌和行为反应缺陷。我们得出结论,大脑中的Sirt1是哺乳动物生长激素信号传导和CR之间的一个联系。