Research Paper Volume 13, Issue 17 pp 21066—21089
Sex-specific differences in DNA double-strand break repair of cycling human lymphocytes during aging
- 1 Department of Obstetrics and Gynecology, Ulm University, Ulm, Germany
- 2 Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
- 3 Institute for Geriatric Research Unit, Agaplesion Bethesda Hospital, Ulm University, Ulm, Germany
Received: June 7, 2021 Accepted: August 10, 2021 Published: September 10, 2021https://doi.org/10.18632/aging.203519
How to Cite
Copyright: © 2021 Rall-Scharpf et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The gender gap in life expectancy and cancer incidence suggests differences in the aging process between the sexes. Genomic instability has been recognized as a key factor in aging, but little is known about sex-specific differences. Therefore, we analyzed DNA double-strand break (DSB) repair in cycling human peripheral blood lymphocytes (PBL) from male and female donors of different age. Reporter-based DSB repair analyses revealed differential regulation of pathway usage in PBL from male and female donors with age: Non-homologous end joining (NHEJ) was inversely regulated in men and women; the activity of pathways requiring end processing and strand annealing steps such as microhomology-mediated end joining (MMEJ) declined with age in women but not in men. Screening candidate proteins identified the NHEJ protein KU70 as well as the end resection regulatory factors ATM and BLM showing reduced expression during aging in women. Consistently, the regulatory factor BLM contributed to the MMEJ proficiency in young but not in old women as demonstrated by knockdown analysis. In conclusion, we show that DSB repair is subject to changes upon aging and age-related changes in DSB repair are distinct in men and women.