WASHINGTON: Scientists have identified a genetic mutation – found in an Indiana Amish family – that may extend life by up to ten years, and are now testing an experimental “longevity” drug that recreates the effect.
The genetic mutation, discovered by Northwestern University in the US in an extended family of Old Order Amish living in the vicinity of Berne, Indiana, appears to protect against multiple aspects of biological ageing in humans.
Indiana Amish kindred with the mutation live more than 10 per cent longer and have 10 per cent longer telomeres (a protective cap at the end of our chromosomes that is a biological marker of ageing) compared to Amish kindred members who do not have the mutation.
Amish with this mutation also have significantly less diabetes and lower fasting insulin levels.
A composite measure that reflects vascular age also is lower – indicative of retained flexibility in blood vessels in the carriers of the mutation – than those who do not have the mutation, the research also found.
These Amish individuals have very low levels of PAI-1 (plasminogen activator inhibitor,) a protein that comprises part of a “molecular fingerprint” related to ageing or senescence of cells.
It was previously known that PAI-1 was related to ageing in animals but unclear how it affected ageing in humans.
“The findings astonished us because of the consistency of the anti-ageing benefits across multiple body systems,” said Douglas Vaughan, from Northwestern University.
“For the first time we are seeing a molecular marker of ageing (telomere length), a metabolic marker of ageing (fasting
insulin levels) and a cardiovascular marker of ageing (blood pressure and blood vessel stiffness) all tracking in the same direction in that these individuals were generally protected from age-related changes,” said Vaughan, lead author of the study published in the journal Science Advances.
“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’,” he said.
Researchers including those from Tohoku University in Japan developed an oral drug, TM5614, that inhibits the action of PAI-1. The drug is already being tested in Japan.
Researchers will apply for approval to start an early phase trial in the US, possibly to begin within the next six months.
The proposed trial will investigate the effects of the new drug on insulin sensitivity on individuals with type 2 diabetes and obesity because of the mutation’s effect on insulin levels in the Amish.
The Amish kindred in Berne, Indiana, have been genetically and culturally isolated and most are at least distantly related.
The ancestors of the Indiana Amish emigrated in the middle of the 19th century from Berne, Switzerland.
The town recalls the architecture of their original home in Switzerland with its Swiss-style clock tower and architecture.
The mutation was introduced into the Amish kindred by farmers from Switzerland, who moved into the area.
Two of their descendants, who carried the mutation, married into the Amish community. The Amish community outside the Berne area does not carry this mutation.
People with the mutation live to be 85 on average, significantly longer than their predicted average lifespan of 71 for Amish in general and which has not changed much over the last century. (AGENCIES)
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