Scientists Discover New Causes of Cellular Decline in Prematurely Aging Children (Progeria); Finding May Shed Light on Normal Aging

In a paper published in the February 20, 2018 issue of Cell Reports, Saint Louis University researchers have uncovered new answers about why cells age in children with a rare and fatal disease, Hutchinson-Gilford Progeria Syndrome (HGPS). The open-access article is titled “A Cell-Intrinsic Interferon-like Response Links Replication Stress to Cellular Aging Caused by Progerin.” The data points to cellular replication stress and a mistaken innate immune response as culprits, and the team found success in the laboratory in blocking these processes with vitamin D. Susana Gonzalo, PhD, Associate Professor of Biochemistry and Molecular Biology at SLU, and her lab examined human and animal cells connected to HGPS. HGPS is caused by the random mutation of a single gene that causes children to age rapidly. Children with the condition develop many of the typical changes and illness associated with aging, including hair loss, aging skin, joint abnormalities, and bone loss. The disease causes atherosclerosis -- fatty deposits that clog arteries -- and patients with the illness die from cardiovascular complications such as stroke or myocardial infarction in their teens. Thanks to genetic mapping, scientists now know that HGPS is caused by a mutation in the LMNA gene, which encodes the lamin A protein. Lamin A serves as a scaffold that keeps the cell's nucleus organized and in shape. The shortened, mutated version of this protein is called progerin, and it causes the nucleus and cell to become unstable, leading to premature aging of the cells. "Those with progeria have a mutation in their DNA that codes for these proteins," Dr. Gonzalo said. "The presence of progerin makes a mess in the nucleus." This is a problem because the nucleus houses our DNA.
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