A key area of our biology targeted for potential interventions to slow down or even reverse aging are the caps on the ends of chromosomes called telomeres. These protective caps become shorter each time a cell divides and over time lead to the “fraying” of DNA and the eventual death of that cell.
One way to prevent this from happening would be to find a way to bolster the activity of an enzyme called telomerase which is responsible for maintaining the structural integrity of telomere caps.
Back in 2015, a group of researchers had discovered a gene called PARN. Under normal conditions, PARN is responsible for processing and stabilising an important component of telomerase called TERC, but when it mutates, the production of the enzyme goes down and telomeres become shortened prematurely.
Now, in continuation of this line of research, Suneet Agarwal – leader of the research group behind the discovery of PARN – and his team from Harvard University have conducted a new study, published in Cell Stem Cell, screening more than 100,000 known chemicals in search of compounds that could preserve the healthy function of PARN.
The tests were performed on stem cells made from the cells of patients with dyskeratosis congenita (DC), a disease which leads to the shortening of telomeres and premature death in roughly 80% of those afflicted.
As luck would have it, Agarwal and his colleagues managed to identify a handful of molecules which they found capable of inhibiting an enzyme called PAP5 that resulted in telomeres being restored to their normal length.
For the next step, necessary to ensure safety, the researchers used human blood stem cells to trigger mutations in the PARN gene to induce dyskeratosis congenita and implanted them into mice. Once treated with the newly discovered compounds, the mice were found to have boosted TERC and normalised telomeres, all without side effects.
“We envision these to be a new class of oral medicines that target stem cells throughout the body,” Agarwal said. “We expect restoring telomeres in stem cells will increase tissue regenerative capacity in the blood, lungs, and other organs affected in DC and other diseases.”