Understanding how the Aging of Germline Cells “Resets” in Offspring

Sean Krivitsky ‘27

Figure 1. Section of a DNA double helix

People have long been fascinated by the process of aging as well as the potential to reverse or prevent it. In particular, ribosomal DNA (rDNA) has been found to potentially play a role in aging. As aging occurs, rDNA repeats in the germline are gradually lost over time, as evidenced by the lab’s work in Drosophila melanogaster. However, this lost rDNA is later replenished in the germline cells of offspring in each generation, which is referred to as rDNA magnification and this allows for germline immortality. Thus, understanding the mechanism by which organisms can replenish lost rDNA in the germline in a new generation will give better insights into how aging works and may even explain a way to combat aging in humans.

A lab recently founded by Dr. Jonathon O. Nelson here at Stony Brook studies the underlying mechanisms responsible for germline immortality. The goal of the Nelson lab is to establish this process of rDNA copy number expansion as involving asymmetric divisions, only happening in germline stem cells and not in differentiating germ cells. A major question surrounding this research was of the validity of the unequal sister chromatid exchange (USCE) model, which suggests that rDNA is lost and gained when sister chromatids unequally exchange rDNA copies, and the extrachromosomal rDNA circles (ERC) reintegration model, which points to intra chromatid recombination and reintegration as a point at which proper rDNA copy numbers are recovered. For one of the lab’s most recent publications, Dr. Nelson took a hybrid approach to answering this question, combining an analysis of Drosophila melanogaster germline cells and computer simulations to investigate changes in rDNA copy numbers in germline cells. Through these different techniques, they were able to support the idea that only germline stem cells are capable of rDNA copy number recovery and they do so through the USCE model, which then allows for germline immortality.

Germline immortality is important for allowing genetic information to be continuously passed on from generation to generation. This recent study by the Nelson lab provides important evidence for the mechanism behind this process of rDNA magnification in Drosophila melanogaster, supporting the idea that rDNA magnification can only be achieved in germline stem cells and is done through the USCE model of rDNA copy number maintenance.

Works Cited

[1] Nelson, J. O., Tomohiro Kumon, & Yamashita, Y. (2023). rDNA magnification is a unique feature of germline stem cells. Proceedings of the National Academy of Sciences of the United States of America, 120(47). https://doi.org/10.1073/pnas.2314440120

[2] Image retrieved from: https://denstoredanske.lex.dk/DNA

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