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Autophagy’s Role in DNA Loss and Survival of Diploid Yeast Cells During Chronological Aging

10-25-2023

“In other words, cells live as long as their genome is restorable, and full DNA content is the limit of life.” 

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BUFFALO, NY- October 25, 2023 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 19, entitled, “Live while the DNA lasts. The role of autophagy in DNA loss and survival of diploid yeast cells during chronological aging.”

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. In this new study, while analyzing the chronological lifespan (CLS) of diploid Saccharomyces cerevisiae cells, researchers Tuguldur Enkhbaatar, Marek Skoneczny, Karolina Stępień, Mateusz Mołoń, and Adrianna Skoneczna from the Polish Academy of Sciences and Rzeszów University 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. The researchers 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. The researchers 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.

“The observations we made in aging research using yeast as the eukaryotic cell model may help to understand the mechanisms that prevent aneuploidy during aging or cancerogenesis in cells where chromothripsis has occurred.”

Read the full paper: DOI: https://doi.org/10.18632/aging.205102 

Corresponding Authors: Adrianna Skoneczna

Corresponding Emails: ada@ibb.waw.pl

Keywords: aging, genome instability, lifespan, autophagy, double-strand breaks

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About Aging-US:

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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