Source: Saint Louis University
Summary: Researchers have uncovered new answers about why cells rapidly age in children with a rare and fatal disease. The data points to cellular replication stress and a mistaken innate immune response as culprits.
Hutchinson-Gilford Progeria Syndrome (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. Researchers from the Saint Louis University have uncovered new answers about why cells rapidly age in children with a rare and fatal disease. 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 Vit- D. The study findings were published in the journal Cell Reports.
Thanks to genetic mapping, scientists now know that HGPS is caused by a mutation in the LMNA gene, which encodes for lamin A protein. 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. The team revealed that replication stress is a key cause of the underlying DNA damage accumulation found in the cells of those with HGPS. Replication stress occurs when the machinery that replicates DNA encounters obstacles along the way that makes replication to stall until the obstacle is removed. They hope that their research not only will help in the eventual development of new therapies for those with HGPS, but that it also will explain many of the processes that underlie normal human aging.
Assoc. Prof. Susana Gonzalo said, “When we block this pathway with vitamin D, it rejuvenates the cells”, “The immune response is activated by progerin and then it is brought back down by vitamin D, as it reduces significantly the toxicity of progerin in cells from HGPS kids.”
More Information: Ray Kreienkamp et al, “A Cell-Intrinsic Interferon-like Response Links Replication Stress to Cellular Aging Caused by Progerin”, Cell Reports (2018). DOI: 10.1016/j.celrep.2018.01.090