Is the Fountain of Youth Amish Genes?


If Peter Thiel wants to live forever, he could be better served to suck the blood of the Amish instead of the young. A new study published in Science Advances illustrates how a particular genetic mutation in an Amish community has given much of the population a longer life, a better metabolism and lower rates of diabetes. The findings could be a blessing to understand longevity in humans and develop methods to increase life expectancy in future generations.

"It's a remarkable natural experiment," said Dr. Douglas Vaughan, a cardiologist at the Northwestern University School of Medicine and co-author of the study. "It gives us a look at new approaches to reduce diseases related to aging and perhaps prolong the healthy life of human beings."

In essence, the study revolves around the proxy measures of the telomeres, the ends of the DNA strands to protect the chromosomes from deterioration or fusion with another chromosome. As the DNA replicates, the telomeres shorten little by little, creating what scientists call senescence (biological aging). As senescence increases, body cells will increase the production of certain proteins more than others, and these proteins can be measured to badess aging in the body.

One of the proteins of use is the plasminogen activator inhibitor-1 or PAI-1. But the role of PAI-1 in human longevity has never been fully understood. Vaughan and his colleagues around the world decided to unravel this mystery.

The team recruited 177 members of the Berne Amish community in Indiana and performed genetic badyzes of each person's copy of SERPINE1, the gene coding for PAI-1. The team found that 43 men and women exhibited a non-functional copy of SERPINE1, and that these carriers lived an average of 10 years longer than others in the same community.

"This mutation of loss of function in SERPINE1 effectively reduces the production of the PAI-1 protein by 50 percent in individuals who carry a copy of the mutation," says Vaughan. "This probably has multifactorial effects that reduce internal signals and the factors that drive senescence in cells and tissues."

None of the participants who possessed the mutated SERPINE1 gene showed signs of diabetes, but 7% with the normal SERPINE1. In addition, the mutated SERPINE1 gene was also correlated with fasting insulin levels lower than the average, which results in a greater capacity to metabolize food and nutrients.

Amish communities are famous and very close, and unique genes can spread through the population in a few generations. According to Vaughan, the SERPINE1 mutation has been approved not through at least seven generations. The average life expectancy of the Berne community, according to the results, is around 75 years, while those with SERPINE1 live to an average age of 85.

The mutation is incredibly rare in the general population, but could There are some ways to use the findings to develop practical interventions that could promote longer lives and healthier lives. "Certainly, we want to revisit relatives and do additional tests to understand the effects on the speed of aging and other changes related to aging," he says. "The fact that Amish with a lifelong PAI-1 deficiency has no apparent negative effects suggests that targeting the protein with a drug could be achieved safely."

Such a drug could be much closer on the horizon than we think. The team led by Dr. Toshio Miyata of Tohoku University in Japan is conducting early phase clinical trials with an orally active PAI-1 blocker. A biotech company called Renascience (based in Tokyo) holds the patent for the drug and has licensed a formulation to a US company called Eirion Therapeutics, who are moving forward to develop a topical preparation for the prevention and treatment of baldness. . . "It turns out that one of the ways in which PAI-1 contributes to aging is by limiting the mobilization and migration of cells, and this can be important in hair growth or lack of it," says Vaughan.

The treatment of baldness is not exactly the source of youth that most of us hope for, but if that drug proves successful and safe, it could be the first step towards making a PAI-1 blocker drug that in reality leads to longer lives. Who would have thought that the Amish had the answer from the beginning?

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