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Gene conferring long-life identified in US Amish community

20 November 2017

By Charlott Repschlager

Appeared in BioNews 927

A rare genetic mutation leading to longer and healthier lives has been discovered in an Amish community in the USA.

Researchers at Northwestern University in Evanston, Illinois, identified the mutation by analysing a gene called SERPINE1 in 177 members of the Old Order Amish community in Berne, Indiana. SERPINE1 codes for the protein PAI-1, which is involved in cell ageing, and also impairs the breakdown of blood clots.

Having two mutated copies of SERPINE1 results in problems with blood clotting, which can lead to excessive bleeding after injury. But having one mutated copy of SERPINE1 gave people a significant health advantage, according to the study published in Science Advances.

These health benefits and increased lifespan were seen in the 43 members of the Amish community who had one normal and one mutated copy of the gene, and as a result had about 50 percent less PAI-1 in their blood. They had lower blood sugar levels between meals, a lower incidence of diabetes and an average lifespan of 85 years - 10 years longer than members of the community with two normal copies of SERPINE1.

People with one mutated copy of the gene also had telomeres that stayed longer into old age. Longer telomeres offer more protection to the DNA and indicate slower ageing of the cells.

It is the first time that these molecular and metabolic markers have been found in a community known for long lives with few age-related illnesses, said Dr Douglas Vaughan, a cardiologist at Northwestern University's Feinburg School of Medicine and lead author of the study.

'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,' Dr Vaughan said.

The protein PAI-1 has already been studied in mice, where lower levels of the protein seemed to protect against age-related diseases and prolonged lifespan. Those results had previously not been confirmed in humans. The relative isolation of the Amish community of Berne means that their naturally lower levels of PAI-1 have been preserved, making them an ideal cohort to study the effects of PAI-1 in humans.

'This is the only kindred on the planet that has this mutation,' Dr Vaughan said. 'It's a "private mutation".'

In the general population PAI-1 levels have been found to dramatically increase in people suffering from obesity, type 2 diabetes or cardiovascular disease. 'We are very optimistic about its potential role not just in slowing ageing but in reducing age-related morbidities,' said Dr Vaughan.

However, geriatrician Dr Nir Barzilai of Albert Einstein College of Medicine in New York City, New York, warned that the data was collected from only one small group of people, Science magazine reported. Nevertheless, researchers at Tohoku University in Japan are trialling a therapy targeting PAI-1 blood levels in humans, despite concerns about potential side effects such as problems with blood clotting.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

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18 March 2013 - by Antony Blackburn-Starza 
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A gene associated with increased lifespan in a number of organisms is now thought to have no effect on longevity after a second look revealed significant flaws in the original studies on which the assumptions were based. The findings will disappoint the manufacturers of many anti-ageing creams that claim to work by activating the gene, but are unlikely to put a stop to research...
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