IMR Press / FBL / Volume 10 / Issue 2 / DOI: 10.2741/1661

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Epigenetic control of telomerase and modes of telomere maintenance in aging and abnormal systems
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1 Department of Biology, University of Alabama at Birmingham, AL 35294-1170, USA
2 Center of Aging, University of Alabama at Birmingham, AL 35294, USA
3 Comprehensive Cancer Center, University of Alabama at Birmingham, AL 35294, USA

Academic Editor: Douglas Ruden

Front. Biosci. (Landmark Ed) 2005, 10(2), 1779–1796; https://doi.org/10.2741/1661
Published: 1 May 2005
(This article belongs to the Special Issue Epigenetic effects during development and disease launch)
Abstract

Epigenetic control provides a mechanism for the reversible silencing of telomerase expression that occurs as a natural consequence of differentiation. Significant overlap between indirect telomerase regulation pathways and cell cycle checkpoint pathways exist, suggesting that these discrete genetic elements (namely, p21, p53, and hTERT) synergistically cooperate to inhibit tumorigenesis. Mutations in these pathways have been known to contribute to cancer formation. However, the incorporation of epigenetic regulatory mechanisms provides another line of defense against these negative occurrences. These proteins are also implicated in the process of senescence, caused in eukaryotic cell lines by telomere shortening. Although the debate continues, there is significant evidence to classify the process of cellular senescence as an in vitro model for human aging. In addition, the study of stem cells gives information about the down-regulation of hTERT in the aging process. Diseases such as Werner S syndrome, ATM (ataxia telangiectasia mutated kinase), DKC (dyskeratosis congenita), and atherosclerosis have been linked to aberrant telomerase expression and other aging-related tissue malfunctions could be related to the presence of senescent cells changing the cellular microenvironment. Therefore, restoring telomerase activity as a putative therapeutic strategy necessitates further study to elucidate the intricacies linking genetic and epigenetic modulations of hTERT.

Keywords
hTERT
Epigenetics
Alternate lengthening of telomeres
Werner syndrome
Senescence
p21
p53
Telomerase recruitment
Review
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