Researchers from the Salk Institute are using induced pluripotent stem cells (IPS cells) to study aging. The cells were induced from patients suffering from Hutchinson-Gilford Progeria Syndrome, an extremely rare (1 in 8 million) genetic disorder that causes premature aging.
This is a 4-year-old boy with Hutchinson-Gilford Progeria Syndrome.Photo: Courtesy of The Progeria Research Foundation
Normal human aging is difficult to study because the lifespan of the average researcher is the same as that of the average patient. No one scientist could follow a group of people from birth to old age. Unless, that is, the people are unfortunate enough to suffer from Progeria, in which case they exhibit the symptoms of accelerated aging and are unlikely to live past the age of 13. Progeria is caused by a single base pair change (point mutation) in the lamin A gene, which results in a defect in their cells' nuclear structure.
The Salk researchers, led by Juan Carlos Izpisúa Belmonte, used cells from Progeria patients to create IPS cells. Since lamin A is not expressed in embryonic stem cells, the transformed IPS cells lacked the hallmarks of the disease. They appeared completely normal and acted like healthy cells. However, when these Progeria IPS cells were allowed to differentiate into smooth muscle cells, the symptoms of Progeria reappeared.
When the Progeria IPS cells were first genetically modified to prevent the expression of lamin A and then allowed to differentiate, the resultant muscle cells did not show signs of premature aging. This means that the researchers could not only use Progeria cells to watch the aging process unfold more rapidly, but they could also control whether or not the cells experienced rapid aging. Besides being a model for normal aging, the Salk scientists hope this study will lead to a potential treatment for Progeria.