The current pace of population aging is without parallel in human history but surprisingly little is known about the human aging process, because life spans of eight decades or more make it difficult to study. Now, researchers at the Salk Institute for Biological Studies have replicated premature aging related disease.
The team report that they have successfully generated induced pluripotent stem (iPS) cells from skin cells obtained from patients with Hutchinson-Gilford Progeria Syndrome—who age eight to 10 times faster than the rest of us—and differentiated them into smooth muscle cells displaying the telltale signs of vascular aging.
Hutchinson-Gilford Progeria Syndrome is caused by a single point mutation in the gene encoding lamin A, which forms a protein scaffold on the inner edge of the nucleus that helps maintain chromatin structure and organize nuclear processes such as RNA and DNA synthesis. The mutation creates an alternative splice site that leads to the production of a truncated version of the protein known as progerin. Unlike the full-length protein, progerin does not properly integrate into the nuclear lamina, which disrupts the nuclear scaffold and causes a host of problems.
Progerin accumulates mainly in smooth muscle cells found within the walls of arterial blood vessels, and vascular smooth muscle cells degeneration is one of the hallmarks of Hutchinson-Gilford Progeria Syndrome-associated arteriosclerosis. In fact, vascular smooth muscle cell senescence also plays a role in advanced arteriosclerosis within the normal aging population.