Aging can be a real downer, but for some individuals premature aging is a lot more serious than a few aches and pains the morning after some touch football. Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic disorder where the victims speed through aging. It is caused by a point mutation in the lamin A gene, involved in nuclear stability, chromatin structure and gene expression. The mutated gene produces progerin, whose accumulation causes various defects, including a disorganized nuclear lamina and loss of heterochromatin.
Fortunately, some talented researchers lead by Juan Carlos Izpisua Belmonte at the Salk Institute for Biological Studies and Center for Regenerative Medicine in Barcelona, have created a stem-cell model for the premature ageing illness that should facilitate aging related studies. They also uncovered some interesting epigenetics action in the process.
The team took fibroblasts from HGPS patients and generated induced pluripotent stem cells (iPSCs). As controls, they produced iPSCs from regular fibroblasts. HGPS-iPSCs didn’t display the nuclear and epigenetic characteristics normally seen with HGPS; in fact, they looked like the iPSCs from the control fibroblasts.
When taking a genome-wide peak at CpG methylation in the fibroblast lines and the subsequent iPSC line, the team found that:
- The iPSC lines had more in common with each other than with the fibroblasts from which they were derived.
- The methylation differences between the two iPSC lines were slight: only 33 genes showed up, unrelated to specific function groups, whereas…
- There were methylation differences in 586 genes between the HGPS and control fibroblasts, mostly associated with genes involved in regulating development and transcription.
When the investigators differentiated the HGPS-iPSCs into specialized cell types, progerin and its aging-related characteristics reappeared suggesting that progerin can induce some significant epigenetic changes.
Since progerin doesn’t just accumulate in premature aging, but also in physiological aging, the model should be useful in studying historically tricky areas like vascular aging.
Head over to Nature February 2011 and pick up the rest of the details.