“If something’s not working, it has to be eliminated”

an interview with Ana Maria Cuervo

Finally! (Issue I/2020)

Mrs. Cuervo, we all know what age looks like. But what is actually happening inside our body when we are getting older?

Ageing is a gradual loss of function at the level of all cells in your body. It’s not a disease, it’s just part of our physiological process. But it increases vulnerability to disease and age-related disorders, that are irritating for the last years of our lives.

At what age do you start ageing from a medical perspective?

Of course you start ageing at the moment you are born. But the kind of ageing we are talking about has a big window of variability. This is very interesting for us scientists, we work a lot with centenarians, people who live for more than hundred years. They don’t start ageing until very late.

There are areas where strikingly many of these centenarians live ...

In Sardinia, for example, or Okinawa in Japan. Initially there was the idea that there might be something in the region, their nutrition or their habits, that was making them live longer. During the last five years that has switched a little, because most of the studies show that these are not people who take very good care of themselves, they often smoke, for example. They can afford to do that because they have good genes. And as we investigate we find there are centenarians in almost every country.

Over the last century, life expectancy increased dramatically around the globe. Why?

This is very associated with medical discoveries. Many used to die of cardiovascular disorders or from infectious diseases. When you don’t have penicillin it doesn’t matter if you have centenarian genes. All the advances in medicine and our way of living helped to prolong our lifespan. But over the last forty years we are not prolonging the time free of disease, what we call healthspan. There has not been any major breakthrough. Our elders are suffering from various disorders, they are not in the condition we would like them to be.

What are the most important diseases of age, are they made by civilization?

Among the major age-related disorders the neurodegenerative conditions are a big concern, like Alzheimer’s and Parkinson’s disease. Then you have the metabolic disorders like diabetes or sclerosis while cancer is a really age-related illness, too. The environmental factors seem to be important. We have dramatically changed our diet in history, that is really compromising our age on a cellular level.

How do the scientist want to deal with this situation?

We are looking for ways to change the the shape we age. You might die but you don’t have this fifteen, twenty years of gradual deterioration. That’s what you can see in centenarians, and that’s what we want: to be healthy and then to drop dead.

In recent years researchers have made revolutionary discoveries in understanding the ageing process on a molecular basis

We still don’t have the perfect way but in the last seven years we found clues on how some cellular processes match the fitness of the person – or our test animal.

Scientists from all the world have started to work together and we came out with nine pillars of ageing, processes that contribute to ageing if they don’t work properly. One of them is telomeres, the tips of your chromosomes. There are very beautiful studies showing how their condition relates to your real age. Or the epigenetic clock: The little flags on your genes can show how old your body is, how much you stressed your insulin production for example. It also shows, that your organs might age differently. The important thing is: Studies show that you can really modulate your age by focusing on these “pillars of ageing”.

What are you doing in your own lab?

We are working on proteostasis, which is the quality control inside your cell. If one part is not working properly, it has to be eliminated. Everyday every one of your cells is cleaning things, that’s extremely important. But unfortunately, as you get old, this cleaning systems don’t work so well. To put it in a context of a disease, my lab studies neurodegenerational disorders like Alzheimer. Normally in those diseases you have a particular protein that is mutated. It’s already there when you are young, but the cleaning system takes it out – till you are around eighty. Then it stops working efficiently and the proteins start affecting your neurons, the symptoms start appearing.

So you want to address different illnesses by working on the basics …

That’s the idea. The risk factor for all of them is really the ageing of the cells. In the last months there have been meetings of geroscientists all around the world, because we think this has to be a global change in the way of thinking. And actually we seem to have found a way of maintaining cellular cleaning very late in life in animal models and they live longer and are healthier. You can check their epigenetic clock to see if our intervention helps – and apparently it does, in an epigenetic level our animals are younger than they are.

How would a visit to the doctor look like in the future?

For each “pillar of ageing” we would have to develop a very simple test, like a blood test, then you can look at this whole package, like your “ageing package”. You might do that in your annual checkup to see how these pillars of ageing are moving. Then you can decide on the intervention, drugs for example. We have many companies that are trying to develop these drugs.

That would be a very individualized treatment. Looking at these amazing possibilities, will they most likely only be available to the wealthy?

It really depends. If we develop drugs you of course do have more access with health insurance. But some of the drugs we are looking at are known substances that are already coming out of patent. For example Metformin, that has so far been used in Diabetes. But forget about drugs, there are so many things at the level of habits you can change! The lower classes always eat more sugar and more fat, because it is cheaper. But for the cleaning moment it is more important when you eat than what you eat. If you are continuously eating the cells don’t have any motivation to clean, which they do if they need energy and have to decide what to burn. Snacking is really killing this process. This way of eating has already become popular in the form of “intermittent fasting”.

What else helps apart from the diet?

Sleep! That something our society is so bad at lately. We are continuously distracted by our phones. But to put it as an image: You don’t clean a store when it is open and mop around the customers, you shut it down first0. Brain cells also are cleaned better when they are less active during the night. It will become important to educate the population about these good habits. The idea is to have at very functional people at a high age, which would be positive for families and the economy. We may have to find a different way to integrate them into society, such as through volunteer work.

Some of your colleagues believe that – in theory – there is no law of nature that limits a lifetime. Humankind’s dream of immortality …

I don’t believe in that. They propose that the regenerative medicine will become so good that you can live as long as you want. Who knows, but I don’t think that we are biologically meant to last forever. Everything has an expiration date.

Interview by Frederike Biron

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