New target identified for treatment of premature aging disease: Scientists discovered that a particular RNA accumulates in people with progeria, and that inhibiting the RNA reverses signs of aging and extends life span in mice

A stretch of DNA that hops around the human genome plays a role in premature aging disorders, scientists at the Salk Institute and King Abdullah University of Science and Technology (KAUST) in Saudi Arabia have discovered. In people with early aging, or progeria, RNA encoded by this mobile DNA builds up inside cells. What’s more, the scientists found that blocking this RNA reverses the disease in mice.

The findings, published in Science Translational Medicine on August 10, 2022, focus on a piece of RNA known as LINE-1.

“These findings provide new insight into progeroid syndromes and how to treat them, while also highlighting the importance of LINE-1 RNA in normal aging,” says co-corresponding author Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory and director of the Altos Labs San Diego Institute of Science.

Progeroid syndromes, which include Hutchinson-Gilford progeria syndrome and Werner syndrome, cause accelerated aging in children and adolescents. Patients develop not only striking physical appearances but also symptoms and diseases typically associated with older age, such as heart disease, cataracts, type 2 diabetes, osteoporosis and cancer. There are currently no effective treatments for progeroid syndromes.

Izpisua Belmonte and his colleagues knew that one of the molecular signatures of both normal aging and progeroid syndromes is the altered overall organization of DNA. When DNA is packaged differently into the nuclei of cells, it changes which genes are accessible for the cell to use and can therefore drastically change a cell’s behavior and function.

Scientists also knew that human genomes contain hundreds of LINE-1 elements that propagate and move around the genome, as well as encode LINE-1 RNA. The function of these elements is poorly understood, but they change and multiply with age, as well as in diseases including cancer and cardiovascular disease. Izpisua Belmonte’s team wondered whether they also changed in progeroid syndromes.

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