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Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity

Telomere shortening or loss of shelterin components activates DNA damage response (DDR) pathways, leading to a replicative senescence that is usually coupled with a senescence-associated secretory phenotype (SASP). Recent studies suggested that telomere aberration that activates DDR may occur, irres...

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Autores principales: Adwan Shekhidem, Huda, Sharvit, Lital, Huffman, Derek M., Manov, Irena, Atzmon, Gil, Shams, Imad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137574/
https://www.ncbi.nlm.nih.gov/pubmed/37107603
http://dx.doi.org/10.3390/genes14040845
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author Adwan Shekhidem, Huda
Sharvit, Lital
Huffman, Derek M.
Manov, Irena
Atzmon, Gil
Shams, Imad
author_facet Adwan Shekhidem, Huda
Sharvit, Lital
Huffman, Derek M.
Manov, Irena
Atzmon, Gil
Shams, Imad
author_sort Adwan Shekhidem, Huda
collection PubMed
description Telomere shortening or loss of shelterin components activates DNA damage response (DDR) pathways, leading to a replicative senescence that is usually coupled with a senescence-associated secretory phenotype (SASP). Recent studies suggested that telomere aberration that activates DDR may occur, irrespective of telomere length or loss of shelterin complex. The blind mole-rat (Spalax) is a subterranean rodent with exceptional longevity, and its cells demonstrate an uncoupling of senescence and SASP inflammatory components. Herein, we evaluated Spalax relative telomere length, telomerase activity, and shelterin expression, along with telomere-associated DNA damage foci (TAFs) levels with cell passage. We show that telomeres shorten in Spalax fibroblasts similar to the process in rats, and that the telomerase activity is lower. Moreover, we found lower DNA damage foci at the telomeres and a decline in the mRNA expression of two shelterin proteins, known as ATM/ATR repressors. Although additional studies are required for understanding the underling mechanism, our present results imply that Spalax genome protection strategies include effective telomere maintenance, preventing early cellular senescence induced by persistent DDR, thereby contributing to its longevity and healthy aging.
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spelling pubmed-101375742023-04-28 Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity Adwan Shekhidem, Huda Sharvit, Lital Huffman, Derek M. Manov, Irena Atzmon, Gil Shams, Imad Genes (Basel) Article Telomere shortening or loss of shelterin components activates DNA damage response (DDR) pathways, leading to a replicative senescence that is usually coupled with a senescence-associated secretory phenotype (SASP). Recent studies suggested that telomere aberration that activates DDR may occur, irrespective of telomere length or loss of shelterin complex. The blind mole-rat (Spalax) is a subterranean rodent with exceptional longevity, and its cells demonstrate an uncoupling of senescence and SASP inflammatory components. Herein, we evaluated Spalax relative telomere length, telomerase activity, and shelterin expression, along with telomere-associated DNA damage foci (TAFs) levels with cell passage. We show that telomeres shorten in Spalax fibroblasts similar to the process in rats, and that the telomerase activity is lower. Moreover, we found lower DNA damage foci at the telomeres and a decline in the mRNA expression of two shelterin proteins, known as ATM/ATR repressors. Although additional studies are required for understanding the underling mechanism, our present results imply that Spalax genome protection strategies include effective telomere maintenance, preventing early cellular senescence induced by persistent DDR, thereby contributing to its longevity and healthy aging. MDPI 2023-03-31 /pmc/articles/PMC10137574/ /pubmed/37107603 http://dx.doi.org/10.3390/genes14040845 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Adwan Shekhidem, Huda
Sharvit, Lital
Huffman, Derek M.
Manov, Irena
Atzmon, Gil
Shams, Imad
Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity
title Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity
title_full Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity
title_fullStr Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity
title_full_unstemmed Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity
title_short Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity
title_sort damage-free shortening of telomeres is a potential strategy supporting blind mole-rat longevity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137574/
https://www.ncbi.nlm.nih.gov/pubmed/37107603
http://dx.doi.org/10.3390/genes14040845
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