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Antioxidants
Special Issues
Role of Telomerase in Aging and Cancer
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Role of Telomerase in Aging and Cancer

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: closed (31 October 2016) | Viewed by 23855

Special Issue Editor

Dr. Gabriele Saretzki

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Guest Editor
Newcastle Institute for Ageing and Institute for Cell and Molecular Biosciences, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE4 5PL, UK
Interests: telomerase in ageing and cancer; TERT in mitochondria; oxidative stress; mitochondria; senescence and ageing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleauges,

Telomerase is a reverse transcriptase with versatile functions. In its canonical and best-analysed role, it maintains telomeres, the end of linear chromosomes. In humans, telomerase activity is downregulated in the majority of somatic tissues with the consequence that telomeres shorten in most cells due to ongoing proliferation, as well as oxidative stress, and thereby contribute to cellular senescence and the ageing process. However, several adult human cell types, such as germline cells, lymphocytes, and endothelial cells, still maintain some telomerase, while adult stem cells can upregulate the enzyme activity when activated from quiescence. Recently, telomerase activators have been developed that might be able to counteract the decrease of telomerase in these cell types and, thus, help to counteract its decrease during the ageing process.

Telomerase with its canonical function is also known to play an important role for cellular transformation and tumorigenesis due to its telomere maintaining role, which is an essential pre-requisite for unlimited proliferation of cancer cells. In addition, there are also various non-canonical, non-telomeric functions known to influence cancer properties. These can be involved in tumor development and progression, the metastasising potential, epithelial-to mesenchymal transition (EMT) and inflammation processes. Due to high, constitutive telomerase activity being an almost universal property of most cancer types, telomerase inhibition has been proposed as a possible new treatment for cancer therapy.

This Special Issue aims at providing an update about the current knowledge and research progress of the fundamental role of telomerase in the processes of aging and cancer biology, as well as possible therapeutic options in both fields. We welcome original manuscripts, as well as review articles, on all these indicated topics.

Dr. Gabriele Saretzki
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Telomerase activity and telomere maintenance in different cell types
  • The role of telomerase during aging and senescence
  • Telomerase activation as an anti-aging strategy
  • Telomerase activity in the development and progression of cancer
  • Telomerase inhibition in cancer cells and tissues
  • Non-telomeric functions of the telomerase protein TERT
  • Subcellular localization of TERT and its interaction with signaling pathways
  • New aspects of telomerase regulation

Published Papers (2 papers)

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Review

439 KiB  
Review
Current Insights to Regulation and Role of Telomerase in Human Diseases
by Mert Burak Ozturk, Yinghui Li and Vinay Tergaonkar
Antioxidants 2017, 6(1), 17; https://doi.org/10.3390/antiox6010017 - 28 Feb 2017
Cited by 52 | Viewed by 10369
Abstract
The telomerase ribonucleoprotein complex has a pivotal role in regulating the proliferation and senescence of normal somatic cells as well as cancer cells. This complex is comprised mainly of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) and other associated proteins that function [...] Read more.
The telomerase ribonucleoprotein complex has a pivotal role in regulating the proliferation and senescence of normal somatic cells as well as cancer cells. This complex is comprised mainly of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) and other associated proteins that function to elongate telomeres localized at the end of the chromosomes. While reactivation of telomerase is a major hallmark of most cancers, together with the synergistic activation of other oncogenic signals, deficiency in telomerase and telomeric proteins might lead to aging and senescence-associated disorders. Therefore, it is critically important to understand the canonical as well as non-canonical functions of telomerase through TERT to develop a therapeutic strategy against telomerase-related diseases. In this review, we shed light on the regulation and function of telomerase, and current therapeutic strategies against telomerase in cancer and age-related diseases. Full article
(This article belongs to the Special Issue Role of Telomerase in Aging and Cancer)
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2355 KiB  
Review
Treating Cancer by Targeting Telomeres and Telomerase
by Marko Ivancich, Zachary Schrank, Luke Wojdyla, Brandon Leviskas, Adijan Kuckovic, Ankita Sanjali and Neelu Puri
Antioxidants 2017, 6(1), 15; https://doi.org/10.3390/antiox6010015 - 19 Feb 2017
Cited by 69 | Viewed by 12694
Abstract
Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: [...] Read more.
Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: hTERT, a catalytic subunit, and hTR, an RNA template whose sequence is complimentary to the telomeric 5′-dTTAGGG-3′ repeat. In humans, telomerase activity is typically restricted to renewing tissues, such as germ cells and stem cells, and is generally absent in normal cells. While hTR is constitutively expressed in most tissue types, hTERT expression levels are low enough that telomere length cannot be maintained, which sets a proliferative lifespan on normal cells. However, in the majority of cancers, telomerase maintains stable telomere length, thereby conferring cell immortality. Levels of hTERT mRNA are directly related to telomerase activity, thereby making it a more suitable therapeutic target than hTR. Recent data suggests that stabilization of telomeric G-quadruplexes may act to indirectly inhibit telomerase action by blocking hTR binding. Telomeric DNA has the propensity to spontaneously form intramolecular G-quadruplexes, four-stranded DNA secondary structures that are stabilized by the stacking of guanine residues in a planar arrangement. The functional roles of telomeric G-quadruplexes are not completely understood, but recent evidence suggests that they can stall the replication fork during DNA synthesis and inhibit telomere replication by preventing telomerase and related proteins from binding to the telomere. Long-term treatment with G-quadruplex stabilizers induces a gradual reduction in the length of the G-rich 3’ end of the telomere without a reduction of the total telomere length, suggesting that telomerase activity is inhibited. However, inhibition of telomerase, either directly or indirectly, has shown only moderate success in cancer patients. Another promising approach of targeting the telomere is the use of guanine-rich oligonucleotides (GROs) homologous to the 3’ telomere overhang sequence (T-oligos). T-oligos, particularly a specific 11-base oligonucleotide (5’-dGTTAGGGTTAG-3’) called T11, have been shown to induce DNA damage responses (DDRs) such as senescence, apoptosis, and cell cycle arrest in numerous cancer cell types with minimal or no cytostatic effects in normal, non-transformed cells. As a result, T-oligos and other GROs are being investigated as prospective anticancer therapeutics. Interestingly, the DDRs induced by T-oligos in cancer cells are similar to the effects seen after progressive telomere degradation in normal cells. The loss of telomeres is an important tumor suppressor mechanism that is commonly absent in transformed malignant cells, and hence, T-oligos have garnered significant interest as a novel strategy to combat cancer. However, little is known about their mechanism of action. In this review, we discuss the current understanding of how T-oligos exert their antiproliferative effects in cancer cells and their role in inhibition of telomerase. We also discuss the current understanding of telomerase in cancer and various therapeutic targets related to the telomeres and telomerase. Full article
(This article belongs to the Special Issue Role of Telomerase in Aging and Cancer)
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