Brown researcher leads $9.8M NIH grant to evaluate whether DNA elements promote aging or age-related diseases

JOHN SEDIVY, a professor of biology and medical science at Brown University, is the lead researcher for a $9.8 million National Institutes of Health grant to study how certain types of movable pieces of DNA may cause age-related diseases. / COURTESY JOHN MACIEL
JOHN SEDIVY, a professor of biology and medical science at Brown University, is the lead researcher for a $9.8 million National Institutes of Health grant to study how certain types of movable pieces of DNA may cause age-related diseases. / COURTESY JOHN MACIEL

PROVIDENCE – Researchers, including John Sedivy, the Hermon C. Bumpus Professor of Biology and a professor of medical science at Brown University, have found that movement within the genome (genetic material) of potentially harmful DNA snippets may cause or contribute to age-related health problems. Thanks to this preliminary work with these DNA snippets, called retrotransposable elements, they received a $9.76 million grant from the National Institutes of Health, for which Sedivy is the lead investigator.

He explained that these elements are akin to parasites – such as a virus or bacterium – that divide and spread to other people. That process is good for the parasite, but bad for the host person, he said, noting that the identical relationship occurs with these elements but only within the confines of the genome. “The [elements] are always trapped in the genome they’re in, but they can move to different parts of the genome,” said Sedivy. “By moving [around], they ensure their survival. It’s kind of bizarre.”

While young people’s strong immune systems effectively fight off bacteria and viruses, and the healing of wounds and broken bones occur rapidly, as we age, our bodies are less efficient in all these areas. It’s no different with these retrotransposable elements, he said, noting that their movements become more active as our old cells’ functions become compromised and can’t quash that motility.

The grant supports research by Sedivy, as well as by Brown University Professor of Biology Dr. Stephen Helfand and researchers at the University of Rochester and New York University, although Brown will receive almost half of the grant funds over the five year life of the grant. Through studying human skin cells, fruit flies and mice, the researchers are evaluating how these elements are held back or held under control in young cells, how those mechanisms break down during the aging process and what damage is inflicted once these elements become active.

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Sedivy said, “Once we find the most promising leads, the issue is: ‘How do we treat this?’ Can we develop drugs against these retrotransposable elements?” HIV is a retrotransposable element and New York University researchers found – and Brown researchers confirmed – that some drugs designed to fight HIV are also effective against our own retrotransposable elements. “We already have a drug; we just have to find a disease to make it effective against,” he said.

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