A tight-knit Amish community in Indiana might hold the secret to longlasting life in their genes. Researchers found that members carrying a key gene mutation lived ten years longer on average than those who lacked the mutation. Some companies are already working on longevity drugs based on the study’s findings.

Credit: Pixabay.

Credit: Pixabay.

Modern health-care and nutrition have vastly improved the human lifespan. Figures published by the Centers for Disease Control and Prevention (CDC) show that babies born in the United States in 1900 had a life expectancy of 50 years. In comparison, Americans born in 2012 have a life expectancy of 78.8 years. In terms of gender, women generally live longer than men, with one in every ten girls born in 2012 expected to live for more than 100 years. All of this is absolutely remarkable progress, but aren’t we nearing a brick wall?

Many scientists researching longevity are now investigating genes with hope that they might find new ways to increase life expectancy at a similar pace to that of the last century. It’s no secret that some people age ‘better’ than others, being less exposed to health risks than their peers despite living in the same environment, eating the same food and so on. It logically follows that the reason must be related to their genes.

One of the main reasons why we biologically age has to do with telomeres — the end of DNA strands which are meant to protect chromosomes from deterioration, functioning like shoelace caps. Every time DNA replicates, the telomeres get a bit shorter leading to what scientists call senescence. As the telomeres get shorter and shorter, cells ramp up production of certain proteins. By measuring the concentration of these proteins, it’s fairly easy to assess the aging process in the body.

One such protein is called plasminogen activator inhibitor-1 or PAI-1 for short. Researchers at Northwestern University’s School of Medicine found that this protein could play a major role in human longevity after they sequenced the genomes of 177 members of the Berne Amish community in Indiana.

Douglas Vaughan, a cardiologist, along with colleagues, determined that 43 of these men and women had a nonfunctional copy of SERPINE1, which is the gene that encodes for PAI-1. The average lifespan of the Berne community is about 75 years — slightly lower than the national average — but those with the SERPINE1 mutation live to a median age of 85.

“This-loss-of-function mutation in SERPINE1 effectively lowers the production of the protein PAI-1 by 50 percent in the individuals that carry one copy of the mutation,” says Vaughan. “This likely has multifactorial effects that reduce the internal signals and factors that drive senescence in cells and tissues, which in turn slows the aging process.”

A lower PAI-1 protein count in their body seems to make individuals more resilient in the face of disease. According to Vaughan and colleagues, Amish with the SERPINE1 mutation had no signs of diabetes as opposed to 7 percent of the Amish individuals with the normal SERPINE1 gene. What’s more, those with the mutation also exhibited a better metabolism and lower-than-average levels of fasting insulin, according to the findings published in Science Advances.

Previously, Israeli researchers identified another gene mutation that extends lifespan, also by ten years, but only in men.

“The findings astonished us because of the consistency of the anti-aging benefits across multiple body systems,” Vaughan said in a statement. “That played out in them having a longer lifespan. Not only do they live longer, they live healthier. It’s a desirable form of longevity. It’s their ‘health span.’”

Since Amish communities are so isolated, it’s fairly easy for unique genes and mutation to become widespread among the population within just a few generations. Amazingly, almost every living Amish can trace their roots to one of 200 German-Swiss immigrants that came to American during the 18th and 19th centuries. The big downside is that the little genetic variance makes the Amish population particularly susceptible to high rates of genetic disorders like dwarfism or development delays. In the general population, however, the SERPINE1 mutation is very rare.

The good news is that some scientists think that you don’t have to be born with such a mutation to reap the longevity benefits. Since there aren’t any apparent negative effects related to PAI-I deficiency, it’s possible to use drugs to target this protein. Already, Japanese researchers Tohoku University are conducting an early phase clinical trial with an orally active PAI-1 blocker. A Japanese company called Renascience holds the patent for the drug which is currently being licensed to Eirion Therapeutics in the United States. There, the drug is marketed as a treatment for baldness since one of the mechanisms by which PAI-1 contributes to aging is by limiting cell mobility, which can be important in hair growth. Besides preventing baldness, the drug might also prolong our lifespan — but that’s something which we won’t discover until the last clinical trials are reported.

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