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

Adva Hadar, Irena Voinsky, Olga Parkhomenko, Monika Puzianowska-Kuźnicka, Jacek Kuźnicki, Illana Gozes, David Gurwitz

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1419-1424
Number of pages6
JournalDrug Development Research
Volume83
Issue number6
DOIs
StatePublished - Sep 2022

Keywords

  • ATM
  • DNA repair
  • centenarians
  • healthy aging
  • lymphoblastoid cell lines
  • miR-181a-5p

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