TY - JOUR
T1 - Higher ATM expression in lymphoblastoid cell lines from centenarian compared with younger women
AU - Hadar, Adva
AU - Voinsky, Irena
AU - Parkhomenko, Olga
AU - Puzianowska-Kuźnicka, Monika
AU - Kuźnicki, Jacek
AU - Gozes, Illana
AU - Gurwitz, David
N1 - Publisher Copyright:
© 2022 The Authors. Drug Development Research published by Wiley Periodicals LLC.
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
KW - ATM
KW - DNA repair
KW - centenarians
KW - healthy aging
KW - lymphoblastoid cell lines
KW - miR-181a-5p
UR - http://www.scopus.com/inward/record.url?scp=85133119830&partnerID=8YFLogxK
U2 - 10.1002/ddr.21972
DO - 10.1002/ddr.21972
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C2 - 35774024
AN - SCOPUS:85133119830
SN - 0272-4391
VL - 83
SP - 1419
EP - 1424
JO - Drug Development Research
JF - Drug Development Research
IS - 6
ER -