A new study, led by Miguel Godinho Ferreira, IGC Alumni, and published in Nature Aging, reveals that by reactivating a specific gene in the cells of the intestine, they were able to increase the life expectancy of zebrafish. The discovery opens prospects for countering aging disorders, cancer, and neurodegenerative disease.

The research started in 2013 when Miguel Godinho Ferreira was at the IGC leading the Telomeres and Genetic Stability laboratory. The research team began to analyze the telomerase zebrafish mutant and proposed it as a premature aging vertebrate model. Miguel explains that “until then, there was only the mouse model, and it did not have human-like short telomeres. We showed that the fish would recapitulate human problems far more accurately”.  Back in dose days, the idea came to Miguel “within the context of understanding organ communication, and the IGC was bubbling with these ideas.”

Miguel is presently leading the research team at IRCAN – the Institute for Research on Cancer and Aging of Nice – and they are studying the effect of telomere length on aging in zebrafish. Telomeres are chromosome ends that shorten over time, playing an essential role in aging. The scientists inserted a DNA fragment into the zebrafish that enabled the intestinal cells to produce an enzyme called telomerase, which lengthens telomeres. By doing this, they were able to slow down the aging of the intestine and the whole organism, leading to increased fertility, better general health, and longer lifespan without an increased risk of cancer.

To learn more about the research, we talked with Miguel and got more answers.

IGC – Could telomeres hold the key to personalized medicine and greater longevity in the future?
Miguel – Sure! We already know of human telomerase deficiencies that cause diseases that share problems of premature aging, such as cancer. We have just shown that cancers that do not express telomerase are more immunogenic and better for immunotherapies.

IGC – What are the potential implications of your findings for understanding and treating aging-related diseases in humans?
Miguel – A crucial aspect of our work is that we can act on a single organ and ameliorate the aging of the entire organism. If we concentrate on treating intestine aging, we may have the same effects in humans. This was proposed by Elie Metchnikoff more than 100 years ago.

IGC – After this discovery, what direction will your research take?
Miguel – Now that we know that the intestine is an initiator organ, we are looking for how it communicates with the rest of the organism. We already have important clues: i) the microbiota of the rescued intestine is more diverse and has the profile of younger individuals, so we think it may contribute to the youth of the animal; ii) we know that the dysfunctional intestine is disrupted and allows for external compounds to enter the bloodstream of the animal. These can be microorganisms or their products and cause chronic inflammation; iii) finally, both the immune and the nervous systems are likely candidates to communicate the health status of the intestine. So, in the future, we will pursue all these hypotheses independently.

 

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