Telomeres are protective DNA sequences that cap the ends of our chromosomes. They don’t code for anything, but instead serve a ‘sacrificial’ purpose. Cells can’t replicate the full length of the chromosome, causing the telomeres to become shorter at each cell division. Telomeres exist in part to prevent important genetic information from being lost. Unfortunately, after a certain number of divisions, there will be no telomeric DNA left, leaving the cell unable to divide further.
This telomere attrition is thought to be one of main drivers of the ageing process and contributes to many age-related diseases. It is particularly problematic for stem cells, which continually divide throughout our lives in order to replace dying cells and repair tissue damage. An enzyme called telomerase is able to repair and extend shortened telomeres, but it isn’t active enough in human cells to counteract telomere shortening. What would happen if we could dial up the production of telomerase in living humans? That’s what several companies hope to investigate, including one called Rejuvenation Technologies.
Rejuvenation Technologies’ experimental treatment uses mRNA (messenger RNA) delivered via lipid nanoparticles. Just as some Covid vaccines use mRNA to trigger the production of spike protein by human cells, this treatment uses mRNA to ramp up the production of telomerase enzymes. This approach has been in development since 2016, and is capable of reversing telomere shortening by around the equivalent of 10 years of cell division. The company is now gearing up towards seeking clinical trial approval.
We know that more rapid telomere shortening is associated with faster ageing in humans, but there’s still some debate regarding to what extent telomere shortening actually causes ageing. Animal studies suggest that genetically increasing telomerase production extends their lifespan and delays age-related diseases. However, we don’t yet have any solid evidence that boosting telomerase affects the ageing process in humans, which is why we need more clinical trials.
Rejuvenation Technology’s treatment has already been tested in mice, rabbits and non-human primates with promising results. The drug appeared to be safe and also appeared to be beneficial in animal models of lung and liver disease. Testing it in humans will still be a slow and difficult process, though. The first step will be small trials in people with specific diseases, with the primary goal being to test whether the treatment is safe. If these are successful, they can proceed to larger trials to assess the effectiveness of the treatment. It’s very hard to get approval for a clinical trial targeting the ageing process itself, so the company will need to pick specific diseases they believe might be treatable through telomere elongation. In other words, the days when we will all be receiving telomere-extending treatments for general age reversal are still far ahead of us.
In addition to the risks associated with testing a lipid nanoparticle therapy (primarily acute immune reactions), we also have to be wary about cancer when testing telomere-extending therapies. Because cell division shuts down when telomeres get too short, they serve as a protective measure against cancer – any rapidly dividing cancer cells will quickly exhaust their telomeres and become unable to divide further.
Some studies have shown that mice get slightly more cancer when telomerase is overexpressed (though they still live longer on average and get fewer diseases besides cancer, so it might be a worthwhile trade-off). However, there may be ways around this. Delivering mRNA only turns up telomerase production transiently, which is something that our stem cells do by themselves anyway. By boosting telomerase expression for just long enough to rebuild our telomeres, we might be able to gain all the benefits of telomere elongation without incurring any additional cancer risk.
Turning Back the Clock With mRNA Telomerase Therapy https://www.lifespan.io/news/turning-back-the-clock-with-mrna-telomerase-therapy/
Rejuvenation Technologies is targeting longevity and age-related disease with telomerase-based mRNA therapies. https://longevity.technology/news/telomere-boosting-mrna-therapeutic-turns-back-the-aging-clock/
Title image by Warren Umoh, Upslash