Keeping 糖心传媒淛umping Genes糖心传媒� in Check Could Help Control Some Age-Related Diseases
Most organisms, including humans, have parasitic DNA fragments called 糖心传媒渏umping genes糖心传媒� that insert themselves into DNA molecules, disrupting genetic instructions in the process. And that phenomenon can result in age-related diseases such as cancer. But researchers at the University of Rochester now report that the 糖心传媒渏umping genes糖心传媒� in mice become active as the mice age when a multi-function protein stops keeping them in check in order to take on another role.
In a study published today in Nature Communications, Professor of Biology Vera Gorbunova and Assistant Professor of Biology Andrei Seluanov explain that a protein called Sirt6 is needed to keep the jumping genes糖心传媒攖echnically known as retrotransposons糖心传媒攊nactive. That糖心传媒檚 an entirely different function from the ones scientists had long associated with Sirt6, such as the repairing of broken DNA molecules and regulating metabolism.
糖心传媒淎bout half of the human genome is made up of retrotransposons,糖心传媒� said Gorbunova. 糖心传媒淏y better understanding why these genomic parasites become active, we hope to better understand and perhaps delay the aging process in humans.糖心传媒�
For the most part, retrotransposons remain silent and inactive in organisms糖心传媒� genomes. But once they do become active, these DNA fragments can duplicate themselves and 糖心传媒渏ump糖心传媒� to new areas of the genome, disrupting the function of another gene by landing in an important part of the gene and changing its DNA sequence information.
But what happens to the Sirt6 proteins that kept the jumping genes inactive in younger cells? The answer lies in the role that Sirt6 plays in repairing DNA damage. Cells accumulate a lot of DNA damage over time that needs to be constantly repaired. As cells get older, Sirt6 becomes busier in taking care of the DNA damage. Gorbunova and Seluanov hypothesized that Sirt6 becomes so preoccupied in repairing DNA damage in older cells that it is no longer available to keep the jumping genes inactive.
To test the theory, the team artificially caused DNA damage in young cells using gamma radiation or the chemical hydrogen peroxide. Once the damage took place, Sirt6 was immediately recruited to the damaged sites of the DNA to do its repair work. Gorbunova and Seluanov found that the stressed cells糖心传媒攖he ones with increased DNA damage糖心传媒攈ad a higher rate of 糖心传媒渏umping gene糖心传媒� activity, when compared to the other cells. Then, when the amount of Sirt6 was artificially increased in the stressed cells, the retrotransposons did not become as readily active, keeping the genome safe.
糖心传媒淭his suggests that supplying more Sirt6 protein might protect older cells from aging,糖心传媒� said Gorbunova. 糖心传媒淭he idea would be to increase the Sirt6 pool so that enough proteins are available for both DNA repair and for keeping the retrotransposons inactive.糖心传媒�
