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A rare mutation found during DNA testing may help further research into new anti-ageing drugs. The gene, called SERPINE1, is thought to be present in up to 5% of the Amish population in Indiana.

SERPINE1 makes a protein called plasminogen activator inhibitor-1 (PAI-1), which may play a role in diabetes and Alzheimer’s. In a typical person, the levels of PAI-1 can be predicted from an individual’s body mass index (BMI). This is because fat, among other things, produces PAI-1. The more visceral fat a person has, the higher the PAI-1 level will be. However, if someone has this rare mutation, the protein levels could decrease to almost nothing.

“This is one of the first clear-cut genetic mutations in human beings that acts upon ageing and ageing-related disease,” Dr Douglas Vaughan told Newsweek. Dr Vaughan, a cardiologist at Northwestern University Feinberg School of Medicine, is one of the lead authors of the study, published in Science Advances [1].

Of further interest is that the Amish community that carried this mutation also seemed to have longer telomeres than those who did not (by about 10%). Telomeres are sections of DNA that cap chromosomes, and scientists think they may protect the rest of the chromosome from damage. Telomere length has also been linked to cellular ageing.

The study was fairly small – only 177 people were tested – and only 43 had the particular mutation that was being studied. The next step is to expand the study, test more people and specifically investigate how the Amish community’s hearing or cognition might change as they age. The long-term aim is to develop a drug that inhibits the protein to provide a similar benefit as the genetic deficiency. Vaughan hopes to bring a clinical trial of the drug to the USA as early as next year.

1. Khan SS, Shah SJ, Klyachko E et al. A null mutation in SERPINE1 protects against biological aging in humans. Science Advances 2017;3(11): DOI: 10.1126/sciadv.aao1617