Sofie Lautrup and Brian C. Gilmour

Earlier this month on the 10th of October and for the ninth year in a row, the Nansen Neuroscience Lecture was held at the Norwegian Academy of Science and Letters (Det Norske Videnskaps-Akademi) in Oslo, arranged by Prof. Jon Storm-Mathisen and Prof. Linda Bergersen.

This year’s invited lecturer was Prof. Morten Scheibye-Knudsen, part of the Center for Healthy Ageing at the University of Copenhagen in Denmark.

Scheibye-Knudsen started his career as a physician in Denmark where he practiced a few years before, much like Nansen himself, he went to Greenland. Unlike Nansen, he did not manage to cross the country on skis but did do a fair amount of biking!

Following his adventures in Greenland, he worked in the laboratory of Prof. Vilhelm A. Bohr at the National Institute on Ageing in Baltimore, USA. Here he studied the importance of DNA repair in ageing and premature ageing, and how DNA repair deficiency can lead or contribute to cognitive deficits.

Scheibye-Knudsen is especially interested in the premature ageing disease Cockayne syndrome, a severe disease showing progressive cognitive dysfunction among others. Scheibye-Knudsen found that in mouse and nematode models of Cockayne syndrome the DNA repair response signaling, known as PARylation (poly ADP-ribosylation), was hyperactive, likely driving the depletion of the cellular energetic factor NAD+, a molecule of special importance at NO-Age.

If Scheibye-Knudsen treated his animal models with an inhibitor of the main PARylating protein, PARP1, he could rescue the phenotype. Additionally, the same effect could be observed by placing the animals on a high fat diet – as good an excuse as any to indulge a bit on our meals!

The results from this change in diet are likely due to an increase in ketogenesis brought on by the diet, mimicking the beneficial effects of other forms of dietary interventions, like fasting and caloric restriction.

Scheibye-Knudsen now has his own research group at University of Copenhagen, where he continues to explore the role of dysfunctional DNA repair in ageing.

His lab makes use of artificial intelligence (AI) to design DNA repair-stimulating compounds and to predict the biological age of animals and patients based on either pictures of human faces, or the movement of a fruit fly. 

His team has identified several compounds, which can stimulate DNA repair without increasing DNA damage, and have observed a positive effect on the lifespan of fruit flies when treated with these drugs. Additionally, Scheibye-Knudsen’s group is identifying new DNA repair-dependent and independent premature ageing diseases using AI: diseases, which they are currently looking more into in the lab.