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How repurposing drugs for healthy ageing could lengthen lifespans

Imagine a drug that could add years on to your life expectancy. Just by taking a pill every day, you might be around for another five or ten years. You might be sceptical: don’t such drugs belong to the realm of science fiction? True, drugs to slow ageing are not yet on the market, but they may be soon. At EPITERNA, a team of 15 people work towards this very goal: finding drugs to extend the lifespans of pets and people. Co-Founder Kevin Perez tells us more.

What’s EPITERNA’s mission?

We want to help pets and people live longer and healthier lives. Our goal is not to double life expectancy, but to prolong lifespan and healthspan – the number of years someone can expect to live in good health. Preventing cancer or cardiovascular disease, for instance, could have a huge impact on your quality of life as you get older. Importantly, it would also reduce costs for our healthcare systems.

Thanks to better health standards, humans live longer than ever before. Do we need drugs to extend our lifespan even further?

Modern medicine is already trying to extend lifespans. If you have hypertension or high cholesterol, you’ll take a drug to prevent early death from these diseases – thus extending lifespan. When we treat cancer, all we’re trying to do is to give a patient more time. The difference is that since ageing is a major risk factor for many conditions, we’re trying to slow it down to prevent these diseases in the first place. Our aim is to offer a drug you can take from a certain age to prevent a plethora of diseases – as opposed to taking drugs to target a disease you already have.

How can this be done?

The concept is simple: we investigate safe, FDA-approved drugs, some of which people are already taking chronically, to test whether they could delay aging and prevent age-related diseases.

Two examples of drugs often associated with slowing down ageing are metformin and rapamycin. The first, typically prescribed to treat type 2 diabetes, works in part by restoring the body’s response to insulin. Epidemiology studies have shown that patients with diabetes taking metformin may have a longer life expectancy than non-diabetic people, but the validity of these studies is still debated. Metformin has also been shown to extend the lifespan of animals like worms and mice, although here again results are mixed.

Rapamycin, meanwhile, is a strong immunosuppressant that’s usually taken by patients who have received an organ transplant. At lower doses, rapamycin may be able to extend lifespan. This has been shown in several animal models, with some of the most notable results seen in mice.

Still, none of these drugs have been shown to extend lifespan in companion animals or humans. With this goal in mind, we investigate the possibility of repurposing drugs to prevent a wider range of diseases and therefore to extend lifespan.

How do you figure out which drugs work?

There are two sides to our work. One involves preclinical research in the lab, where we work with yeast, worms, flies, fish and mice. If we find a new or existing drug that extends their lifespan, this might later be translated to clinical research on pets and humans.

The second aspect of our work is clinical research. Right now, we’re focusing closely on dogs. We’re preparing a clinical trial for 2024 that will involve giving a large cohort of dogs a drug to test whether it can prevent multiple age-related diseases and extend lifespan.

Lifestyle and drugs can work hand in hand to give us the best chance of a healthy and long life.

In a few years’ time, how do you hope to be changing the lives of people and pets?

A lot of research on ageing has been done over the past few decades, but not much has been translated into clinical settings in ways that concretely help people. In fact, so far, no drug has been approved specifically to prevent age-related diseases or extend lifespan. Instead, most drugs are approved to cure or prevent specific diseases.

EPITERNA’s goal for the next five years is to commercialise the first drug to help prevent age-related diseases and extend lifespan. This could come quicker for dogs than for humans, but it would be a huge milestone. There are many misconceptions around drugs to slow ageing, and an approved drug in pets would help people understand how they work and pave the way for accepting such drugs for human use further down the line.

How does this fit in to a time where personalised medicine is all the rage?

We’re swimming against the tide in this respect. Instead of developing a drug tailored to a specific patient, we’re looking to develop a single drug that can be used by anyone – as long as there aren’t any contraindications, of course. The main criterion would be someone’s age. One of our tasks will be to determine from what age the drug should be taken. The patient would then take this drug every day for the rest of their life, with the aim of living longer and healthier. Of course, this long-term treatment means that we need a drug with an extremely good safety profile.

Do you still advocate for healthy lifestyle choices, or could the ‘problem’ of ageing be solved entirely by drugs?

We absolutely encourage healthy living. Lifestyle choices have an enormous impact on how long and well we live. We can drastically influence our lifespans by avoiding risk factors like smoking and drinking, having a healthy diet, being active and sleeping well.

Our idea is to include healthy ageing drugs on top of these basic recommendations. For example, smoking is a big risk factor for heart disease, so you should avoid smoking. But there are also drugs – for hypertension, cholesterol etc. – that help to prevent heart disease. Lifestyle and drugs can work hand in hand to give us the best chance of a healthy and long life.

What’s the biggest challenge for companies like yours?

In preclinical trials, we see that drugs – some of which are already approved and prescribed – can extend the lives of animals. But demonstrating how they do so is another matter. When regulatory agencies assess a new medicine, they want to understand the mechanism that makes it work, but in the field of ageing this can be very hard to prove.

This is because ageing is a complex phenomenon, as a glimpse at Carlos López-Otín’s hallmarks of ageing makes clear. An array of complex, overlapping physiological processes affect how we age, all influenced by a host of different lifestyle and genetic factors. Demonstrating the precise effects a drug has on lifespan is therefore a challenge, compounded by the long and costly nature of clinical trials.

To complicate matters further, no drug has been approved specifically to slow down ageing. Getting the first one approved entails additional layers of regulatory complexity. But I’m optimistic. If we can clearly demonstrate that a drug is safe and helps us live longer – and I believe we will – why would it not be approved and prescribed?

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Kevin Perez
Co-Founder and Head of Research at EPITERNA

Kevin Perez is Co-Founder and Head of Research at EPITERNA. He specialises in ageing biology and computational biology. Prior to founding EPITERNA, he investigated the best strategies and modalities to tackle ageing, notably at the Buck Institute for Research on Aging in Novato, California. Kevin holds an engineering degree from Ecole des Mines, France, and a PhD from Paris Cité University.


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