On November 15th, an article published in Science Advances revealed a special genetic mutation that causes blood clotting defects, but can extend life expectancy for 10 years! At the same time, it slows down aging and reduces the incidence of diabetes. .
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Twenty years ago, a girl from the Berne Amish tribe in Indiana almost died in a routine operation because of excessive blood loss. But now, a cardiologist from the Northwestern University's Feinberg School of Medicine, Douglas Vaughan, led the team to study the patient and other people in her tribe to find the root cause of the accident - the mutation, and confirmed Mutations can extend life!
a rare genetic mutation
Scientists have found in the genome analysis of girls that two copies of one of the genes SERPINE1 have been mutated. This gene encodes plasminogen activator inhibitor type 1 (PAI-1), a key protein responsible for blood clotting.
Previous studies have shown that PAI-1 is an important component of aging-related secretions and directly regulates cell senescence. Moreover, PAI-1 levels in patients with obesity, type 2 diabetes, or cardiovascular disease are significantly higher than in normal subjects. Mice with abnormal expression of PAI-1 protein show signs of premature aging, and targeted inhibition of PAI-1 protein prevents aging and prolongs life cycle.
These results imply that PAI-1 may be a key factor in catalyzing cellular senescence. But the role of PAI-1 in human longevity is not clear.
Extend life and reduce the risk of diabetes?
Douglas Vaughan suspects that in addition to blood clotting, the SERPINE1 gene has other functions. He led the team to conduct research on 177 tribal residents, including girls.
The results showed that most people in the Amish tribe carry the SERPINE1 gene mutation, but very few of the two copies have been mutated. The researchers performed physiological tests on 43 participants with a copy mutation and compared them with those with normal genes in the tribe.
The results show that when carrying a copy of the SERPINE1 mutation, the average life expectancy can reach 85 years, 10 years longer than other normal people in the Horde! "This involves a potential protective effect." Human geneticist Andrew Johnson explained, "SERPINE1 Mutations in the gene lead to healthier metabolic indicators that greatly reduce the probability of diabetes."
Questioning and hope?
Nir Barzilai, a geriatrician at the Albert Einstein School of Medicine in New York, disagreed with this achievement. His team has also discovered a gene mutation that regulates growth hormone sensitivity, which can extend life expectancy for 10 years. But this is limited to men. Barzilai said that the SERPINE1 results were from a small sample, and the genes discovered by their team were validated in all four groups. Therefore, he believes that SERPINE1 is not a convincing longevity gene.
In this regard, Douglas Vaughan believes that more evidence needs to be obtained from clinical trials. It is reported that a Japanese research team is conducting a clinical study of “blocking PAI-1 protein†to test its value in treating people at high risk for diabetic nephropathy. Vaughan believes that targeting SERPINE1 gene-expressing proteins can also lead to new therapeutic approaches for obesity and age-related metabolic diseases.
But is this strategy safe considering the importance of blood coagulation proteins? The researchers believe that when a copy mutation occurs, people still have a normal coagulation mechanism, so blocking PAI-1 does not cause serious consequences. But Andrew Johnson is not sure that the researchers can guarantee the right amount of inhibition so that it doesn't affect health. Undoubtedly, this requires more research work.
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