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Higher ATM expression in lymphoblastoid cell lines from centenarian compared with younger women

With increased life expectancies in developed countries, cancer rates are becoming more common among the elderly. Cancer is typically driven by a combination of germline and somatic mutations accumulating during an individual's lifetime. Yet, many centenarians reach exceptionally old age withou...

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Autores principales: Hadar, Adva, Voinsky, Irena, Parkhomenko, Olga, Puzianowska‐Kuźnicka, Monika, Kuźnicki, Jacek, Gozes, Illana, Gurwitz, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545764/
https://www.ncbi.nlm.nih.gov/pubmed/35774024
http://dx.doi.org/10.1002/ddr.21972
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author Hadar, Adva
Voinsky, Irena
Parkhomenko, Olga
Puzianowska‐Kuźnicka, Monika
Kuźnicki, Jacek
Gozes, Illana
Gurwitz, David
author_facet Hadar, Adva
Voinsky, Irena
Parkhomenko, Olga
Puzianowska‐Kuźnicka, Monika
Kuźnicki, Jacek
Gozes, Illana
Gurwitz, David
author_sort Hadar, Adva
collection PubMed
description With increased life expectancies in developed countries, cancer rates are becoming more common among the elderly. Cancer is typically driven by a combination of germline and somatic mutations accumulating during an individual's lifetime. Yet, many centenarians reach exceptionally old age without experiencing cancer. It was suggested that centenarians have more robust DNA repair and mitochondrial function, allowing improved maintenance of DNA stability. In this study, we applied real‐time quantitative PCR to examine the expression of ATM in lymphoblastoid cell lines (LCLs) from 15 healthy female centenarians and 24 younger female donors aged 21–88 years. We observed higher ATM mRNA expression of in LCLs from female centenarians compared with both women aged 21–48 years (FD = 2.0, p = .0016) and women aged 56–88 years (FD = 1.8, p = .0094. Positive correlation was found between ATM mRNA expression and donors age (p = .0028). Levels of hsa‐miR‐181a‐5p, which targets ATM, were lower in LCLs from centenarians compared with younger women. Our findings suggest a role for ATM in protection from age‐related diseases, possibly reflecting more effective DNA repair, thereby reducing somatic mutation accumulation during aging. Further studies are required for analyzing additional DNA repair pathways in biosamples from centenarians and younger age men and women.
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spelling pubmed-95457642022-10-14 Higher ATM expression in lymphoblastoid cell lines from centenarian compared with younger women Hadar, Adva Voinsky, Irena Parkhomenko, Olga Puzianowska‐Kuźnicka, Monika Kuźnicki, Jacek Gozes, Illana Gurwitz, David Drug Dev Res Research Articles With increased life expectancies in developed countries, cancer rates are becoming more common among the elderly. Cancer is typically driven by a combination of germline and somatic mutations accumulating during an individual's lifetime. Yet, many centenarians reach exceptionally old age without experiencing cancer. It was suggested that centenarians have more robust DNA repair and mitochondrial function, allowing improved maintenance of DNA stability. In this study, we applied real‐time quantitative PCR to examine the expression of ATM in lymphoblastoid cell lines (LCLs) from 15 healthy female centenarians and 24 younger female donors aged 21–88 years. We observed higher ATM mRNA expression of in LCLs from female centenarians compared with both women aged 21–48 years (FD = 2.0, p = .0016) and women aged 56–88 years (FD = 1.8, p = .0094. Positive correlation was found between ATM mRNA expression and donors age (p = .0028). Levels of hsa‐miR‐181a‐5p, which targets ATM, were lower in LCLs from centenarians compared with younger women. Our findings suggest a role for ATM in protection from age‐related diseases, possibly reflecting more effective DNA repair, thereby reducing somatic mutation accumulation during aging. Further studies are required for analyzing additional DNA repair pathways in biosamples from centenarians and younger age men and women. John Wiley and Sons Inc. 2022-06-30 2022-09 /pmc/articles/PMC9545764/ /pubmed/35774024 http://dx.doi.org/10.1002/ddr.21972 Text en © 2022 The Authors. Drug Development Research published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Hadar, Adva
Voinsky, Irena
Parkhomenko, Olga
Puzianowska‐Kuźnicka, Monika
Kuźnicki, Jacek
Gozes, Illana
Gurwitz, David
Higher ATM expression in lymphoblastoid cell lines from centenarian compared with younger women
title Higher ATM expression in lymphoblastoid cell lines from centenarian compared with younger women
title_full Higher ATM expression in lymphoblastoid cell lines from centenarian compared with younger women
title_fullStr Higher ATM expression in lymphoblastoid cell lines from centenarian compared with younger women
title_full_unstemmed Higher ATM expression in lymphoblastoid cell lines from centenarian compared with younger women
title_short Higher ATM expression in lymphoblastoid cell lines from centenarian compared with younger women
title_sort higher atm expression in lymphoblastoid cell lines from centenarian compared with younger women
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545764/
https://www.ncbi.nlm.nih.gov/pubmed/35774024
http://dx.doi.org/10.1002/ddr.21972
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