Dementia research news - spring 2018

4. Amish fountain of youth?


The Berne Amish community is a secluded population living in north-east Indiana in the US. Isolated groups such as these are of great interest to geneticists. Their members tend to remain close-knit, rarely marrying outside the group. This means that unusual inherited features – which could make someone more or less likely to develop a disease – are more likely to be carried in the genes of both parents. These genetic features are then far more likely to be passed down to later generations than they would be otherwise.

Researchers from Chicago’s Northwestern University tested 177 people from the Berne Amish community and found that some had inherited one mutated copy of a gene called SERPINE1 along with one normal copy. People who had the mutated copy of this gene lived an average of 10 years longer than their neighbours who didn’t have it. As well as living longer, the researchers noticed that these people were less likely to have type 2 diabetes or dementia compared to those without the mutated gene.

The body uses the SERPINE1 gene to make a protein called PAI-1. During normal ageing, cells in the body receive signals from PAI-1 telling them to function very slowly. These slowed-down cells build up around the body and are part of the process that results in ageing. In people who have a mutated copy the SERPINE1 gene, PAI-1 is turned off, so there is nothing telling their cells to slow down.

However, there is a downside. PAI-1 also works to stop the breakdown of blood clots. Most people with a mutated copy of SERPINE1 also had a normal copy, meaning they still had half the usual amount of PAI-1 working in their bodies. For people who had two mutated copies of the gene – and no normal copy – there was no PAI-1 in their blood at all. This causes a bleeding disorder where their blood cannot clot properly when needed.

This tells us that the benefits of PAI-1 – reducing the effects of ageing and the risk of type 2 diabetes and dementia – must be weighed against the risk of causing a bleeding disorder. Trials are already underway in Japan, where researchers are using an existing diabetes drug called metformin that they hope can be used to gently ‘turn down’ the amount of PAI-1 in the blood.