To prevent cell death caused by DNA damage, adult brain cells in fruit flies produce extra copies of their chromosomes

Scientists from U-M Molecular, Cellular, and Developmental Biology have discovered a novel anti-aging defense in the brain cells of adult fruit flies: producing extra copies of the genome.

The findings could help explain how the brain, which rarely produces new cells, is able to cope with the accumulation of cell damage over time and prevent excess cell loss during aging. They may also help scientists answer questions about human age-related brain diseases.

Most cells have two copies of each chromosome, one from each parent. This provides each cell with two complete copies of DNA, referred to as the genome. But some cells accumulate extra copies of chromosomes, although how and why they do this is not entirely clear. Some scientists have suggested that excess chromosomes might lead to age-related brain diseases.

“The brain of the fruit fly Drosophila melanogaster is an ideal model for studying age-related changes in the brain because the fly has a relatively short lifespan, its brain cells rarely multiply, and we have excellent tools for manipulating fly genetics,” said lead author Shyama Nandakumar, who just completed her doctorate in Associate Professor Laura Buttitta's group.

In the study, Nandakumar and colleagues examined adult fly brain cells and found that some accumulate extra copies of their genome, especially in parts of the brain responsible for vision—the region of the brain which shows more DNA damage with age.

Next, they subjected fly brain cells to oxidative stress or ultraviolet radiation, which damage DNA and can cause cell death. They found that this exposure increased the production of extra copies of chromosomes in the cells, and the cells were less likely to die as a result of the damage.

“These data suggest that cells with extra copies of the genome are more resistant to cell death and may serve a beneficial or protective role in the aging brain,” Nandakumar said.

Previous studies have found that patients with early stages of Alzheimer’s disease have extra chromosomes in their brain cells than people of the same age who do not have the condition. This has led scientists to question whether accumulating extra chromosomes leads to brain cell death and brain disease.

“Our study suggests that the production of extra copies of chromosomes might actually be a normal response to the accumulation of age-related damage in flies and may even help protect against cell death,” said senior author Laura Buttitta. “Further studies are now needed to determine if this is also true in humans.”

The study is published in eLife. Olga Grushko, U-M senior research technician in internal medicine, is also a co-author.

--U-M News article by Morgan Sherburne