Posted on 20 April 2022
Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.
Why is this research important: Chronic diseases of ageing account for the majority of human deaths, with heart disease and cancer alone responsible for nearly half of yearly deaths around the world. Modern medicine is quite good at keeping people with these chronic diseases alive for longer than ever before but has made comparatively little progress toward developing satisfactory cures. Geroscientists seek to target the fundamental biology of ageing that is ultimately responsible for the development of all age-related diseases, thereby delaying their onset and allowing us to live in good health for longer.
The discovery of a drug that delayed ageing by just one year would have a massive impact on public health. Unfortunately, regulatory bodies like the FDA don’t consider such a clinical outcome as grounds for approval, partly because a consensus about how to test these drugs in humans hasn’t been reached. This may quickly change if clinical trials can demonstrate that existing drugs, already approved for other conditions, are able to delay the onset of age-related diseases.
What did the researchers do: In this review, researchers analysed scientific publications in search of FDA-approved drugs that had been shown to extend lifespan in rodents. They then developed a points-based system in which drugs were ranked according to their estimated probability of success in a well-controlled human clinical trial. Factors affecting the ranking included effects on lifespan, healthspan (the number of years spent in good health), impact on hallmarks of ageing (the nine proposed fundamental drivers of ageing), and mortality. Using this system, the researchers were able to give each drug/drug class a score out of 12.
Key takeaway(s) from this research: Above is a table showing the score breakdowns for the nine highest-ranked drugs the researchers identified. The best score was given to a relatively new class of drugs called SGLT-2 inhibitors. These are compounds used to control blood sugar in patients with type II diabetes. They work by reducing the amount of glucose (sugar) reabsorbed by the kidneys, but the authors of the study note that these drugs seem to have beneficial effects on mechanisms involved in the ageing process. These include boosting the function of the cell’s power plants (the mitochondria), the cell’s waste disposal system (autophagy), and preventing the activation of a ‘pro ageing’ signalling molecule called mTOR.
Other notable compounds include metformin and acarbose (two more type II diabetes treatments), rapamycin (originally developed as an antifungal antibiotic but currently used as an immune suppressant), and methylene blue (a dye that is sometimes used as an antidote to certain toxins).
Currently, the only compound being tested in a serious, large scale clinical trial to determine whether it can delay onset of age-related diseases is metformin. The TAME (Targeting Aging with Metformin) trial will last 6 years and involves over 3,000 individuals between the ages of 65-79. We absolutely need more trials like TAME to investigate other promising approved drugs that could be repurposed, as some of the drugs listed here could fail to show significant benefit. Furthermore, some scientists believe that metformin is not the most promising drug that could have been chosen for a large trial. Methods for ranking compounds like the one developed here may help draw attention to those drugs most likely to find success.
Geroscience-guided repurposing of FDA-approved drugs to target aging: A proposed process and prioritization: https://doi.org/10.1111/acel.13596