PROVIDENCE, R.I. [Brown University] — A National Institutes of Health grant expected to total more than $16 million over five years will fund research into potential causes of Alzheimer’s disease and neurodegeneration, and assist a team of scientists in the search for targets to inform therapeutic strategies to treat those conditions.
With support from a prior NIH grant, the team of biologists from Brown University, New York University and the University of Rochester has been researching the mechanisms of aging with special attention to potentially harmful DNA snippets called retrotransposable elements (or retrotransposons). Evidence from this team and from other scientists has implicated retrotransposons in promoting aging.
With the new NIH funding, the research team will join colleagues from the Salk Institute for Biological Studies to focus specifically on how retrotransposons contribute to neurodegeneration and Alzheimer’s disease.
“For the past five years, we worked on discovering how retrotransposons promote aging,” said principal investigator John Sedivy, a professor of biology and medical science at Brown, and director of the University’s Center on the Biology of Aging. “While these mechanisms are universal and occur in many different types of cells, it’s important to understand variation in cell response. In the renewal phase of this grant, we will investigate how the cells of the central nervous system — neurons, astrocytes, microglia — respond to the detrimental challenges posed by retrotransposons.”
In addition to his role in Brown’s Division of Biology and Medicine, Sedivy is affiliated with the University’s Carney Institute for Brain Science, which is home to a range of clinical and research efforts focused on the causes and treatments for Alzheimer’s and other neurodegenerative diseases.
Retrotransposons are parasitic strands of genetic material that use a copy-and-paste mechanism to replicate and move within the human genome — with mostly harmful consequences. When the first NIH grant was awarded to the team in 2016, the retrotransposon theory of aging was still new. Sedivy was among the researchers who had shown in 2013 that aging cells lose their ability to defend against transposons, resulting in a decline in cell function. In 2019, the team published studies in the journals Nature and Cell Metabolism showing that an HIV drug could halt harmful retrotransposon activity in old cells, significantly reducing age-related inflammation and other signs of aging in mice (which led to an ongoing clinical trial funded by the Alzheimer’s Association). In 2021, the team published a review article in Nature discussing the latest research on retrotransposons.