Scientists at Northwestern University discovered a genetic mutation in an isolated Amish population that seems to slow the aging process, prevent diabetes, and avert other aging-related health concerns. Their discovery led to the development of drug they anticipate will mimic the same effects.
The mutation was discovered in an Amish extended family (or "kindred") living in Berne, Indiana, part of a community that has largely remained genetically isolated for over a century. Carriers were found to live on average 10 percent longer (about 14 years) than those without, be significantly less likely to develop diabetes and have much healthier vascular systems into old age.
The mutation had been documented previously, though for unrelated reasons:
Certain members of this Old Order Amish community were found to have issues with severe bleeding after injuries. In the early 1990s a young girl almost died from excessive bleeding after bumping her head, and on examination she was found to have a rare bleeding disorder on account of a PAI-1 deficiency. Further tests on her immediate family found that the condition was genetic.
Once the correlation was made between PAI-1 deficiency and anti-aging, researchers went about studying the families to understand how and why the mutation operates.
To do so, the researchers set up a temporary facility in a community center and ran a series of tests on 177 Amish people from the community. This included echocardiograms, systolic blood pressure, pulse wave velocity and pulmonary function tests. Urine, blood and fibroblast samples were also taken from participants.
Now, partnering with a Japanese company called Renascience, the researchers are working on drugs that will inhibit PAI-1, in hopes of harnessing the anti-aging capabilities:
Phase 1 human trials have recently been completed in Japan, where the drug was given to 160 people and proved to be safe and nontoxic. The researchers say that the drug should be safe as long as it only partially inhibits the protein – you don't want to end up with excessive bleeding, after all. Phase 2 trials are now underway, with a focus on whether reduced PAI-1 has an effect on how stem cells migrate out of bone marrow.