From Amish Genes to Anti-Aging: A Novel Approach to Longevity
Zoe Biosciences is leveraging knowledge of an Amish genetic mutation with profound implications for life extension and the delay of aging. By comparing the health and lifespan of those who possess the gene mutation and their non-carrier counterparts, the team uncovers valuable insights into the relationship between genetics, healthspan, and human longevity.
The Origin of the Story: An Intriguing Amish Mutation
Scott Gies, Zoe Biosciences’ CEO, offers an intricate narrative about a young Amish woman suffering from a rare bleeding disorder. Further investigations led to the discovery of a null mutation in SERPINE1, the gene coding for the protein PAI-1, which regulates clotting, stem cell migration, and fibrosis. This genetic mutation led to an absence of the PAI-1 protein, thus explaining the woman’s condition.
Notably, this development wasn’t an isolated case for the Amish community in Berne, Indiana. Continued research revealed thousands of “heterozygotes” who had a single copy of the gene mutation and hence, a 50% level of circulating PAI-1. Additionally, about ten “homozygotes” were found, similar to the young woman, carrying the mutation from both parents.
This unique genetic makeup was not merely a benign anomaly, but an epiphany shedding light on the connection between genetics and life extension.
The Longevity Connection: PAI-1 Levels and Biological Aging
Gies discusses the remarkable revelation stemming from the genetic findings – carriers of the mutation, both homozygotes and heterozygotes, showed signs of delayed biological aging. With an average longer lifespan of a decade compared to their counterparts who did not carry the mutation, the carriers also demonstrated superior health advantages.
From a broader perspective, Gies pins the Amish phenomenon as a “natural experiment”. Within the community’s homogenous lifestyle, the only notable variable was the presence or absence of the gene mutation – offering an experimental group and control group for a thoroughly unique investigation.
PAI-1: Creating the Blueprint for Optimal Longevity
High PAI-1 levels in humans are deemed suboptimal for longevity, and the protein is linked closely to cellular senescence, being a prominent marker and intermediary. Utilizing the mutation model, there are hopes to redefine healthspan via newly created therapeutic interventions, potentially creating a new gold standard for delayed human aging.
Zoe Biosciences is working to use PAI-1 inhibitors across multiple modalities and disease indications to model the enhanced longevity seen within Berne’s Amish community. Additionally, efforts are being made to explore other biological targets connected to the unique aging profile of the Amish.
The Promise of Healthspan Expansion and Aging Delay
Amid ongoing research into levers of longevity, the team at Zoe Biosciences emphasizes the objective of redefining healthspan—how many years are spent in good health. By harnessing genetic insights from the Amish community and translating them into therapeutic strategies, transformation in life quality and life extension may soon become a reality for a broader patient population
Key Takeaways
- An Amish gene mutation in SERPINE1 leads to lower circulating levels of PAI-1 protein, linked to clotting, stem cell migration, and fibrosis.
- Carriers of the mutation, both homozygotes and heterozygotes, show delayed biological aging and enjoy a longer, healthier life compared to non-carriers.
- The homogenous Amish lifestyle provides a unique environment for investigating the impact of the gene mutation on healthspan and longevity.
- Zoe Biosciences aims to deploy PAI-1 inhibitors as a therapeutic strategy for extending healthspan and delaying aging.
- The ultimate goal is enhancing the quality of life and its length, serving hundreds of millions of patients with a redefined concept of healthspan.
Source Citation: https://longevity.technology/news/leveraging-the-past-to-illuminate-longevity-for-the-future/
