Nutrition researcher Johan Auwerx uses modern techniques in molecular biology at the EPFL to study how metabolic processes affect health and ageing. "The aim is to die young, but as late as possible," explained the EPFL professor who was awarded the Prix Marcel Benoist in 2016.

Johan Auwerx was surprised to be honoured with the prestigious Swiss science prize: "It is good recognition of the research that I have been doing in Switzerland for nine years," the Belgian added. In the scientist's opinion, the most important difference between the modern world and life 150 years ago is not aviation, nuclear weapons or the Internet, "it is life span." The average life expectancy has risen from 40 to almost 80. "Whereas we used to have one lifetime, now we have two." And the illnesses set in with the second one.

Johan Auwerx, Professor at EPFL, has been awarded this year’s Marcel Benoist Prize. (Photos: Kellenberger Kaminski Photographie)

Johan Auwerx's advice for enjoying a good quality of life after 50 is to "keep your mitochondria in good shape." The mitochondria are the powerhouses of the body's cells – bacteria within our cells, which are responsible for the production of energy. They deliver the energy that enables the heart to beat, the muscles to contract and the brain or stomach to work properly. The organelle, which only measures one micrometre (a millionth of a metre), occurs identically in virtually all human, animal and plant cells. Auwerx and his research group at the EPFL are studying the signal networks, which control the function of the mitochondria, thereby regulating the metabolism in good health, ageing and illness.

"There is only one organelle in our body that has to work constantly – the mitochondrion," explained the scientist "because nothing works without energy." Persistent stress leads to the degeneration of the mitochondria, as the researchers demonstrated on the basis of studies on threadworms and mice. Under the microscope you can follow how young worms, which are only a day old, fidget, whereas there is barely any movement from ten day-old specimens, "like an 80-year old who no longer plays in the garden," explained Johan Auwerx.

Enlarging the motor

The scientist enjoys reading historical documents and explained how the Italian humanist Luigi Cornaro discovered back in the 16th century that it is healthy to eat less. Auwerx knows that "if you restrict the input of calories, the mitochondria become more active." This was confirmed by tests with mice. The animals with the active mitochondria did not only live longer, they did not become ill either.  Johan Auwerx is sure that what is true for the mice also applies to humans; "everything works better with more active mitochondria – from the liver to the muscles to the brain". As has recently been discovered, it also helps prevent depression.

An examination of muscle stem cells.

However, simply eating less food is rarely practicable. Therefore, researchers are pursuing other strategies for increasing the activity of mitochondria. One possibility is biogenesis. "That means producing more new mitochondria," explained Johan Auwerx, comparing the procedure with trading in a Citroën 2CV for a BMW. "It makes you perform better, longer and quicker." In their studies, the researchers demonstrated that two naturally occurring substances stimulate the formation of new mitochondria in threadworms and mice. The scientist explained that "these compounds enlarge the motor". One named resveratrol is contained in red wine, while the other, nicotinamide riboside, equates to vitamin B3 and is contained in milk.

However, the researchers experimented at much higher doses than those which occur naturally. "You would have to drink 50,000 bottles of red wine for this to have an effect," Johan Auwerx explained. The same is true of nicotinamide riboside in milk. "We often work with natural products; however, the quantities in which they occur in food do not have any significant effect." Therefore, the researchers extract the compounds and synthesise the active ingredients in order to use them in greater doses. Following successful testing in animals, there are now plans to conduct clinical trials. The researchers suspect that nicotinamide riboside would be suitable for treating young people who are suffering from Duchenne muscular dystrophy. "We cannot cure the disease," said the scientist, "but perhaps it can delay the deterioration of their muscle function."

Following Nietzsche and Rasputin

Johan Auwerx's second strategy for activating mitochondria is inspired by Nietzsche's quote "that which does not kill us, makes us stronger".  The Russian itinerant preacher Grigori Rasputin is also supposedly an example. He is said to have survived a number of attempted poisonings. "Nowadays, we have antibiotics everywhere, producing super bacteria which are resistant to everything," said the researcher. "Mitochondria are also bacteria which can be made more resistant with the help of antibiotics." This is a concept that initially attracted criticism from his peers. The EPFL professor admits that "it appears counter-intuitive because we are actually using poison. However, it works with worms and mice."

Matteo Cornaglia examines threadworms as test animals.

The research group is now making arrangements to conduct clinical trials on people. The tricky part is the dosage of antibiotics because a class of substances which are particularly toxic has proved to be effective.  In this case, Johan Auwerx does not hold with the argument that results from animal testing are not transferrable to humans. This argument would ring true if there were many proteins in our body, which do not occur in mice. "However, mitochondria have lasted over the course of evolution from primitive organisms through to people," the scientist revealed, "enabling us to make predictions on the basis of our research."

Recycling thanks to pomegranates

In addition to the production of more or stronger mitochondria, the EPFL team has developed a third strategy for countering the effects of ageing: recycling the damaged organelle. When mitochondria are damaged in the course of a person's life, harmful by-products are released. Yoshinori Ohsumi from Japan was awarded the Nobel Prize for Medicine in 2016 for the discovery of mechanisms for the degradation and recycling of cellular components. This process which is known as autophagy, which comes from the Greek "auto" (self) and "phagein" (devouring), also occurs in mitochondria. In mitophagy, damaged mitichondria are removed and used as building blocks for new organelle.

As the researchers in Lausanne discovered, the process can be supported by a naturally occurring compound.  The substance is contained in a fruit, which has been a symbol of fertility since ancient times, the pomegranate. "The extract extended the lives of the worms and improved the lives of the mice," explained Johan Auwerx. However, the compound does not occur in the red seeds, it is in the surrounding white skin or husk.

Therefore, you would have to drink pomegranate juice to benefit from this. However, once again, the dose used in the experiments was far in excess of the amount that you could consume naturally. In addition, there has to be a certain bacteria in the intestines in order to release the correct component. "That bacterium is only present in half of the population," explained Auwerx. He has not tested whether he is one of those people. "I do not take any of that, nor any other supplements for that matter," revealed the 58-year old. "I feel well, and a healthy diet is sufficient for me for the time being. Perhaps that will change when I am a bit older."