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Dear Colleagues,

This Special Issue is the continuation of our 2017 Special Issue “Role of Telomeres and Telomerase in Cancer and Aging”, 2019 Special Issue " Role of Telomeres and Telomerase in Cancer and Aging 2019" and 2020 Special Issue "Role of Telomeres and Telomerase in Cancer and Aging 2020".

Telomeres and telomerase have been receiving ever-increasing interest from the scientific community. This includes biologists deciphering the complex mechanisms and interactions between the different components of telomeres and telomerase, as well as clinicians aiming to use telomere lengths as a biomarker for aging and diseases. Ever more details emerge about the tightly-regulated interaction of telomerase activity in the regulation of telomere lengths, and many mechanisms still remain a mystery, ready to be solved.

Telomerase activity is under tight physiological regulation in human tissues, where the enzyme is active in only a few adult tissues, such as endothelial cells and lymphocytes, but can be upregulated in many types of adult stem cells. Telomere shortening has been associated with cellular senescence and the aging process, as well as major diseases, such as atherosclerosis, obesity, and cardiovascular disease. It is thus of high clinical relevance and is often measured in easily-accessible blood monocytes. By contrast, telomerase activity is highly upregulated and associated with tumorigenesis by maintaining telomeres and thereby constituting an important prerequisite for the ongoing proliferation of cancer cells. Our growing understanding of the mechanisms of telomerase upregulation during cancer development might help in tumor prognosis and in the development of new anticancer treatments and therapies.

In addition, many telomere-independent functions for the telomerase reverse transcriptase protein TERT have been discovered, which add to the complexity of telomerase and the multitude of its functions. It also extends the function of telomerase in its noncanonical role to cell types such as neurons, and organs such as the brain.

The aim of this Special Issue is to demonstrate and share new results and growing knowledge about the roles of telomeres and telomerase during processes such as aging and cancer development.

Prof. Dr. Gabriele Saretzki
Guest Editor

Manuscript Submission Information

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Keywords

telomere length
telomerase activity
TERT
TERC
shelterin
stem cells
dyskerin
cellular senescence
aging
cancer

Published Papers (2 papers)

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Research

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24 pages, 4031 KiB

Open AccessArticle

Methylation of Subtelomeric Chromatin Modifies the Expression of the lncRNA TERRA, Disturbing Telomere Homeostasis

by Diego Oliva-Rico, Eunice Fabian-Morales, Rodrigo E. Cáceres-Gutiérrez, Adriana Gudiño, Fernanda Cisneros-Soberanis, Julieta Dominguez, Oscar Almaraz-Rojas, Cristian Arriaga-Canon, Clementina Castro-Hernández, Carlos De la Rosa, José L. Reyes and Luis A. Herrera

Int. J. Mol. Sci. 2022, 23(6), 3271; https://doi.org/10.3390/ijms23063271 - 18 Mar 2022

Cited by 1 | Viewed by 2389

Abstract

The long noncoding RNA (lncRNA) telomeric repeat-containing RNA (TERRA) has been associated with telomeric homeostasis, telomerase recruitment, and the process of chromosome healing; nevertheless, the impact of this association has not been investigated during the carcinogenic process. Determining whether changes in TERRA expression are a cause or a consequence of cell transformation is a complex task because studies are usually carried out using either cancerous cells or tumor samples. To determine the role of this lncRNA in cellular aging and chromosome healing, we evaluated telomeric integrity and TERRA expression during the establishment of a clone of untransformed myeloid cells. We found that reduced expression of TERRA disturbed the telomeric homeostasis of certain loci, but the expression of the lncRNA was affected only when the methylation of subtelomeric bivalent chromatin domains was compromised. We conclude that the disruption in TERRA homeostasis is a consequence of cellular transformation and that changes in its expression profile can lead to telomeric and genomic instability. Full article

(This article belongs to the Special Issue Role of Telomeres and Telomerase in Cancer and Aging 2022)

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Review

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14 pages, 1673 KiB

Open AccessReview

CRISPR/Cas: A New Tool in the Research of Telomeres and Telomerase as Well as a Novel Form of Cancer Therapy

by Mahendar Porika, Radhika Tippani and Gabriele Christine Saretzki

Int. J. Mol. Sci. 2022, 23(6), 3002; https://doi.org/10.3390/ijms23063002 - 10 Mar 2022

Cited by 4 | Viewed by 3393

Abstract

Due to their close connection with senescence, aging, and disease, telomeres and telomerase provide a unique and vital research route for boosting longevity and health span. Despite significant advances during the last three decades, earlier studies into these two biological players were impeded by the difficulty of achieving real-time changes inside living cells. As a result of the clustered regularly interspaced short palindromic repeats (CRISPR)-associated system’s (Cas) method, targeted genetic studies are now underway to change telomerase, the genes that govern it as well as telomeres. This review will discuss studies that have utilized CRISPR-related technologies to target and modify genes relevant to telomeres and telomerase as well as to develop targeted anti-cancer therapies. These studies greatly improve our knowledge and understanding of cellular and molecular mechanisms that underlie cancer development and aging. Full article

(This article belongs to the Special Issue Role of Telomeres and Telomerase in Cancer and Aging 2022)

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