scholarly journals The reduction of SIRT1 in livers of old mice leads to impaired body homeostasis and to inhibition of liver proliferation

Hepatology ◽  
2011 ◽  
Vol 54 (3) ◽  
pp. 989-998 ◽  
Author(s):  
Jingling Jin ◽  
Polina Iakova ◽  
Yanjun Jiang ◽  
Estela E. Medrano ◽  
Nikolai A. Timchenko
Keyword(s):  
Old Mice ◽  
2008 ◽  
Vol 283 (38) ◽  
pp. 26169-26178 ◽  
Author(s):  
Guo-Li Wang ◽  
Elizabeth Salisbury ◽  
Xiurong Shi ◽  
Lubov Timchenko ◽  
Estela E. Medrano ◽  
...  
Keyword(s):  
Old Mice ◽  

2009 ◽  
Vol 29 (14) ◽  
pp. 3867-3880 ◽  
Author(s):  
Jingling Jin ◽  
Guo-Li Wang ◽  
Xiurong Shi ◽  
Gretchen J. Darlington ◽  
Nikolai A. Timchenko

ABSTRACT Aging reduces the regenerative capacities of many tissues. In this paper, we show a critical role of the glycogen synthase kinase 3β (GSK3β)-cyclin D3 pathway in the loss of the regenerative capacity of the liver. In young animals, high levels of growth hormone (GH) increase expression of GSK3β, which associates with cyclin D3 and triggers degradation of cyclin D3. In livers of old mice, the GSK3β promoter is repressed by C/EBPβ-histone deacetylase 1 (HDAC1) complexes, leading to the reduction of GSK3β. The treatment of old mice with GH increases expression of GSK3β via removal of the C/EBPβ-HDAC1 complexes from the GSK3β promoter. We found that the GSK3β-cyclin D3 pathway is also altered in young GH-deficient Little mice and that treatment of Little mice with GH corrects the GSK3β-cyclin D3 pathway. We present evidence that GSK3β regulates liver proliferation by controlling growth-inhibitory activity of C/EBPα. The downregulation of GSK3β in young mice inhibits liver proliferation after partial hepatectomy via the cyclin D3-C/EBPα pathway, while the elevation of GSK3β in old mice accelerates liver proliferation. Thus, this paper shows that GSK3β is a critical regulator of liver proliferation and that the reduction of GSK3β with age causes the loss of regenerative capacities of the liver.


Author(s):  
Frank A. Rawlins

Several speculations exist as to the site of incorporation of preformed molecules into myelin. The possibility that an autoradiographic analysis of cholesterol-1,2-H3 incorporation at very short times after injection might shed some light in the solution of that problem led to the present experiment.Cholesterol-1,2-H3 was injected intraperitoneally into 24 tenday old mice. The animals were then sacrificed at 10,20,30,40,60,90,120 and 180 min after the injection and the sciatic nerves were processed for electron microscope autoradiography. To analyze the grain distribution in the autoradiograms of cross and longitudinal sections from each sciatic nerve myelin sheaths were subdivided into three compartments named: outer 1/3, middle 1/3 and inner 1/3 compartments.It was found that twenty min. after the injection of cholesterol -1.2-H3 (Figs. 1 and 2), 55% of the total number of grains (t.n.g) found in myelin were within the outer 1/3 compartment, 9% were within the middle 1/3 and 36% within the inner 1/3 compartment


Nature ◽  
2003 ◽  
Author(s):  
HelenR. Pilcher
Keyword(s):  

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