• Fewer calories for better living: Kroemer receives the 2019 Lombardy is Research Award

Healthy Ageing, the Region’s Jury aims for the discovery that will increase longevity

Guido Kroemer received the 2019 International “Lombardy is Research” Award, the award promoted by the Lombardy Region that grants €1 million to the best scientific discovery in the field of Life Sciences, chosen by a Jury of 15 top international scientists. This year's theme is Healthy Ageing.

Kroemer revealed one of the most important mechanisms for increasing longevity: autophagy. He also identified a category of nutritional and pharmacological autophagy inducers, “caloric restriction mimetics”, and demonstrated their usefulness in support of “Healthy ageing”.

Born in Germany, with Austrian and Spanish citizenship, Guido Kroemer is a Professor of Medicine at the University of Paris Descartes, the director of the “Apoptosis, Cancer and Immunity” research team for the French Medical Research Council (INSERM), and the director of “Metabolomics and Cell Biology platforms of the Gustave Roussy Comprehensive Cancer Center”.

Once the winner had been selected by the Jury, which was chaired by Silvia Priori, Professor of Cardiology at the University of Pavia and Director of Molecular Cardiology at IRCCS Maugeri, his name was announced by the Vice President of the Lombardy Region and Councillor for Research, Innovation, University, Export and Internationalization,Fabrizio Sala.

Guido Kroemer discovered a key factor for longevity in caloric restriction, which is capable of inducing autophagy. The researcher developed the concept of “caloric restriction mimetics” (CRMs) by identifying and characterizing natural or pharmacological substances capable of inducing autophagy, in order to combat cardiovascular ageing and improve anti-tumour immunity. He also showed that a naturally occurring polyamine in food, spermidine, increases human longevity.

The ramifications for the territory

“The ‘Lombardy is Research’ award helps increase the Lombardy Region’s leadership in the field of research,” commented Attilio Fontana, President of the Lombardy Region. “I am pleased that the researchers on the Jury have expressed so much appreciation for this initiative. As I’ve always said, investing in Research and Innovation is the right way to look to the future. Since not much is invested in this sector in Italy, the Region’s commitment in this direction will continue and, once we succeed in obtaining Autonomy, we’ll make use of even more resources in order to expand the initiative,” he concluded.

“This award is in recognition of a discovery of global significance that will have a concrete impact on improving people’s lives in terms of healthy ageing,” Vice-President Sala added. “One of this Award’s objectives is for Lombard research centres and medical practices to establish lasting relationships of collaboration and scientific interaction with the winner. For this reason, the Jury has determined thatat least 70% of the Award should be allocated to research activities to be conducted in collaboration with the Lombardy Region’s centres of excellence” concluded Sala, congratulating the winner Guido Kroemer.

The researcher will receive the award on 8 November at the Scala Theatre in Milan, during the 2019 “Research Day” event dedicated to the memory of Umberto Veronesi. Click here to register for the event.

The winner: a weapon to protect cells

Guido Kroemer accepted the Award, stating: “It was 2005 when we published our first paper demonstrating thatautophagy is capable of protecting cells against toxicity, like chemotherapy. We have been conducting this research for 14 years, bearing witness to the fact that all scientific projects require long-term in-depth commitment”.

Kroemer stated that he was ready to collaborate with the research centres of Lombardy.

The Jury’s reasons

The discovery has a direct impact upon the prolongation of people’s healthy ageing, and the underlying research shows how caloric restriction activates mechanisms that degrade altered proteins, thus keeping the body healthier. The jury’s aim was to identify a basic research project that was as close as possible to clinical application, which in fact will lay the groundwork for the future development of drugs capable of slowing down the ageing process.

The details of the discovery

Autophagy is the mechanism by which our body’s cells identify the ‘waste’ inside themselves, or rather their mechanisms and functions that have since become old and altered, and selectively eliminate them in order to free up material useful for reconstructing new, younger, and better functioning structures.
Guido Kroemer discovered that autophagy is one of the secrets to longevity.
The fact that autophagy often occurs in cells that have been subjected to lethal stress, prior to their final disintegration, has long fuelled the hypothesis that autophagy is a cellular suicide mechanism.

However, at his laboratory in Paris, cell biologist Guido Kroemer discovered that autophagy, induced by caloric restriction, does not contribute to cell death. In fact, autophagy actually reduces the cells’ propensity to commit suicide via apoptosis. This observation gave rise to the theory that autophagy is a cellular protection mechanism that safeguards cellular integrity and helps repair structures damaged by external or internal stress.

Indeed, Guido Kroemer discovered that the genetic induction of autophagy increases the longevity of a worm known as Caenorhabditis elegans. This discovery and the ensuing research and partnerships have given rise to more fundamental evidence. For example, the discovery that spermidine, a naturally occurring polyamine in food, has the ability to induce autophagy in various representative models of evolution: yeast, C. elegans, the common fruit fly (Drosophila melanogaster), the mouse, and human cells cultured in vitro. The discovery that the chronic ingestion of spermidine increases the longevity of various model organisms by inducing autophagy was of fundamental importance.

Based on these findings, a general rule was able to be deduced:autophagy is not just a cellular protection mechanism, but it also has a powerful anti-ageing effect.

Guido Kroemer postulated the existence of “caloric restriction mimetics" (CRMs), compounds that mimic caloric restriction. As inhibitors or activators of enzymes with very different structures, CRMs can act in similar ways to mimic the beneficial effects of the low-calorie regime. Overeating and obesity, on the other hand, inhibit autophagy. By deactivating the main anti-ageing mechanism, obesity accelerates biological ageing and leads to the early onset of metabolic syndrome and age-related diseases.

Kroemer has shown that a range of different CRMs (hydroxycitrate, resveratrol, spermidine, and others) increase the immune system’s ability to control tumour growth by inducing autophagy in cancer cells. Hydroxycitrate blocks the development of lung cancer, while resveratrol prevents intestinal cancer.
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