Abstract
The loss of regenerative capacity of tissues is one of the major characteristics of aging. Liver represents a powerful system for investigations of mechanisms by which aging reduces regenerative capacity of tissues. The studies within last five years revealed critical role of epigenetic silencing in the inhibition of liver proliferation in old mice. These studies have shown that a number of cell cycle proteins are silenced in livers of old mice by C/EBPalpha-HDAC1-Brm complex and that old liver fails to reduce the complex and activate these genes in response to proliferative stimulus such as partial hepatectomy. The complex modifies histone H3 on the promoters of c-myc and FoxM1B in the manner which prevents expression of these genes. Despite this progress, little is known about mechanisms by which aging causes this epigenetic silencing. We have recently discovered signal transduction pathways which operate upstream of the C/EBPalpha-HDAC1-Brm complex. These pathways involve communications of growth hormone, GSK3beta and cyclin D3. In addition to the liver, GH-GSK3beta-cyclin D3 pathway is also changed with age in lung, brain and adipose tissues. We suggest that other age-associated alterations in these tissues might be mediated by the reduced levels of GSK3beta and by elevation of cyclin D3. In this review, we summarize these new data and discuss the role of such alterations in the development of aging phenotype in the liver and in other tissues.
Highlights
AGING, June 2009, Vol.1 No.6 transcription and translation [1]
Several recent papers have found that the inhibition of liver proliferation in old mice is associated with formation of multi-protein C/EBPα-Brm complexes in nucleus [6, 7] and multi-protein complexes of RNA binding protein CUGBP1 with translation initiation factor eIF2 in cytoplasm [8, 9, 10]
It has been later shown that the activation of CUGBP1 in livers of old mice leads to the translational elevation of a chromatin remodeling protein histone deacetylase 1, HDAC1, which joins the C/EBPα-Brm complex and silences promoters of the cell cycle genes [10]
Summary
AGING, June 2009, Vol.1 No.6 transcription and translation [1]. This review discusses age-associated mechanisms of inhibition of liver proliferation in the light of this recent finding. Several recent papers have found that the inhibition of liver proliferation in old mice is associated with formation of multi-protein C/EBPα-Brm complexes in nucleus [6, 7] and multi-protein complexes of RNA binding protein CUGBP1 with translation initiation factor eIF2 in cytoplasm [8, 9, 10].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
