Genetic Mutation in Blood Clotting Gene Linked to Longevity

Overview of Aging and Chronic Diseases

A recent study delves into the relationship between a genetic mutation in a blood clotting gene and longevity. Aging is a significant risk factor for numerous chronic conditions, including type 2 diabetes and cardiovascular disease. As the population of elderly individuals expands, the occurrence of age-related diseases similarly increases. Researchers are investigating the molecular mechanisms of aging, suspecting that genetic mutations and cellular alterations contribute. However, effective therapies aimed at slowing aging and enhancing longevity remain elusive.

Gene Involvement in Age-Related Conditions

Prior research has identified the protein plasminogen activator type 1 (PAI-1), produced by the SERPINE1 gene, as a contributor to age-related diseases. Elevated levels of PAI-1 are observed in individuals with obesity, type 2 diabetes, or cardiovascular conditions. Consequently, scientists proposed that a mutation resulting in the loss of function of SERPINE1 might influence human longevity.

Study of Amish Community and SERPINE1 Mutation

A study conducted in the United States, published in Science Advances, assessed 177 individuals from an Amish community in Indiana, known for harboring mutations in the SERPINE1 gene. While everyone possesses two copies of this gene, researchers found that 43 participants had one mutated and one normal copy, with a few others having two faulty copies.

Participants with one mutated copy of SERPINE1 exhibited longer telomeres, which are DNA sequences that protect chromosome ends. As aging progresses, telomeres diminish in length. On average, Amish individuals with one mutated copy had telomeres that were 10% longer and demonstrated lower insulin levels, indicating improved metabolic health.

Impact on Lifespan

Utilizing family histories and death records, the researchers determined that individuals carrying one copy of the mutation had a median lifespan of 85 years, which is 10 years longer than their peers in the community.

Limitations of the Mutation

While one mutated copy of SERPINE1 appears to confer benefits related to aging, having two mutated copies is detrimental. Individuals with two faulty copies lack a crucial blood clotting protein and experience severe bleeding when injured.

Future Research Directions

Scientists are initiating clinical trials for a molecule that inhibits PAI-1, which may offer potential treatment for age-related metabolic disorders. However, experts caution that while the SERPINE1 mutation is not a definitive solution to aging, it may provide valuable insights for researchers examining the aging process.

References

(1) Leslie, Mitch. Mutation in blood clotting gene may extend human life span. Science. November 15, 2017. http://www.sciencemag.org/news/2017/11/mutation-blood-clotting-gene-may-extend-human-life-span. Accessed November 20, 2017.
(2) Khan SS, Shah SJ, Klyachko E, et al. A null mutation in SERPINE1 protects against biological aging in humans. Sci. Adv. 2017; 3:eaao1617.