Better longevity for some Amish people with the SERPIN 1 gene

Researchers from the Indiana Hemophilia & Thrombosis Center (IHTC) from the Northwestern University have uncovered a very rare genetic mutation among an Amish community in the United States. The mutation would be responsible for a 10-years increase in lifespan, compared to those lacking the mutation as well as the national average of 75 years.

A longer and healthier life thanks to SERPIN 1

Genetic testing of 177 subjects among an Amish community in Berne, Indiana, showed 43 carriers of the SERPIN 1 gene mutation, leading to its inactivation [1]. The population displaying the mutation was heterozygous for it, which means that the SERPINE-1 gene was expressed in its mutated form and in its normal form. The carriers of the mutation seemed to live an average of 10 years longer than non-carriers, had lower risks of developing diabetes and cardiovascular diseases, and would have telomeres 10% longer than average. We now know that telomeres can be directly linked to the biological age. 

The role of the PAI-1 protein

The SERPIN 1 gene codes the PAI-1 protein, which is synthesized in fat and liver tissue and helps regulating the dissolution of blood clots in the circulatory system. This protein could be regulated by p53 [2], an important protein in the aging process. The higher the PAI-1 levels are in the body, the more it will show signs of biological aging – and vice-versa, the aging process will be slower in people with low levels of PAI-1, like the Amish with the SERPIN 1 gene [1]. Since gene transmission is hereditary, the researchers were able to confirm that telomere length would, for the most part, be hereditary as well [1].

This is the first study linking PAI-1, longer telomeres and life expectancy, with the conclusion that PAI-1 could directly influence life expectancy. Many studies will be conducted to better understand the phenomenon, such as a detailed study of PAI-1 action on reducing telomere length, and a study of a PAI-1 inhibiting molecule, TM-5614 [1].

Sources : 

[1] Sadia S.Khan, Sanjiv S.Shah, Ekaterina Klyachko,…Douglas E. Vaughan, A null mutation in SERPINE1 protects against biological aging in humans (2017), Science Advances Vol 3 n°11
[2] Roderik M Kortlever, Paul J. Higgins and René Bernards, Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence (2006), Nature Cell. Biol 2006 Aug 8, 877-884