By Allison Proffitt
September 2, 2009 | Researchers in Singapore have connected a “housekeeping gene” to a premature aging disorder affecting skin and bone with some brain components. Their research was published in the September 1 issue of Nature Genetics.
Bruno Reversade and his colleagues at the Institute of Medical Biology and collaborators in Germany tested saliva samples from families suffering from a congenital disorder causing prematurely wrinkled and sagging skin or “wrinkly skin syndrome”. Using the Affymetrix SNP chip, the team mapped the region to chromosome 17. Then, “By high-throughput sequencing of the entire candidate region, we detected disease-causing mutations in the gene PYCR1,” the authors said. The technique yielded 50x coverage, Reversade told Bio-IT World. “You have an enriched and highly purified fraction of the genome, which you’re targeting,” he said.
“What’s unexpected,” he explains, “is that it’s an enzyme that was discovered many years ago. It’s almost a housekeeping gene and no one would expect it would lead to aging in human. This is a surprise and where the mystery lies.”
The scientists found that the PYCR1 protein is located in mitochondria and causes changes in mitochondrial morphology and cell death in the connective tissues of individuals with PYCR1 mutations. The findings, "unexpectedly highlight the importance of metabolism as PYCR1 is important in the synthesis of proline, a common amino acid involved in metabolism,” says Reversade.
In addition, Reversade and his colleagues found that patients with wrinkly skin syndrome were also lacking the corpus callosum, the structure connecting the two hemispheres of the brain. This was another surprising finding that Reversade intends to explore further.
Reversade said he has heard some interest in translating these results to the treatment of normal aging. “We’ve been contacted by several big pharma,” he says. “I don’t know if they want to buy notoriety by being linked to the discovery—I’m not into doing cosmetic [science]—but [proline metabolism] is a tempting target.” He theorizes, “Maybe there are polymorphisms in the population that would account for people’s ability to age faster or slower.”