Research Paper Volume 15, Issue 19 pp 9965—9983

Live while the DNA lasts. The role of autophagy in DNA loss and survival of diploid yeast cells during chronological aging

Tuguldur Enkhbaatar1, , Marek Skoneczny1, , Karolina Stępień2, , Mateusz Mołoń3, , Adrianna Skoneczna1, ,

  • 1 Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw 02-106, Poland
  • 2 Institute of Medical Sciences, Rzeszów University, Rzeszów 35-959, Poland
  • 3 Institute of Biology, Rzeszów University, Rzeszów 35-601, Poland

Received: June 13, 2023       Accepted: September 6, 2023       Published: October 9, 2023
How to Cite

Copyright: © 2023 Enkhbaatar 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.


Aging is inevitable and affects all cell types, thus yeast cells are often used as a model in aging studies. There are two approaches to studying aging in yeast: replicative aging, which describes the proliferative potential of cells, and chronological aging, which is used for studying post-mitotic cells. While analyzing the chronological lifespan (CLS) of diploid Saccharomyces cerevisiae cells, we discovered a remarkable phenomenon: ploidy reduction during aging progression. To uncover the mechanism behind this unusual process we used yeast strains undergoing a CLS assay, looking for various aging parameters. Cell mortality, regrowth ability, autophagy induction and cellular DNA content measurements indicated that during the CLS assay, dying cells lost their DNA, and only diploids survived. We demonstrated that autophagy was responsible for the gradual loss of DNA. The nucleophagy marker activation at the start of the CLS experiment correlated with the significant drop in cell viability. The activation of piecemeal microautophagy of nucleus (PMN) markers appeared to accompany the chronological aging process until the end. Our findings emphasize the significance of maintaining at least one intact copy of the genome for the survival of post-mitotic diploid cells. During chronological aging, cellular components, including DNA, are exposed to increasing stress, leading to DNA damage and fragmentation in aging cells. We propose that PMN-dependent clearance of damaged DNA from the nucleus helps prevent genome rearrangements. However, as long as one copy of the genome can be rebuilt, cells can still survive.


CFU: colony forming units; CLS: chronological lifespan; DSB: double-strand break; NHEJ: non-homologous end joining; PFGE: pulse-field gel electrophoresis; PI: propidium iodide; PMN: piecemeal microautophagy of nucleus; RLS: replicative lifespan.