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Trial Lecture – time and place
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Adjudication committee
- First opponent: Professor Manuel Zimmer, University of Vienna, Austria
- Second opponent: Professor Katja Kanninen, University of Eastern Finland,
- Third member and chair of the evaluation committee: Associate professor Hua Hu, University of Oslo
Chair of the Defence
Professor Magnar Bjørås, University of Oslo
Principal Supervisor
Associate Professor Evandro Fei Fang, University of Oslo
Summary
Autophagy and NAD+ as key players in dietary restriction, health and aging
Calorie restriction or, the reduction of energy intake without malnutrition, has been a topic of great interest in the field of biogerontology since 1935. Since then, hundreds of articles have shown in several animal species that a pronounced reduction in caloric intake results in a significant increase in both lifespan and healthspan.
The aims of the thesis were to further understand the molecular mechanism by which dietary restrictions increase the healthspan and lifespan, and test whether combining dietary restriction with dietary supplementation could ameliorate some of the side-effects from dietary restriction.
The cellular process of autophagy was assessed, and it was found that the overexpression of a single autophagic gene in neurons can double the maximum lifespan of C. elegans. In addition, increased stress resistance and health at old age was also observed.
Furthermore, the molecular pathway was further elucidated by knockdown other autophagy-related genes. The interactions between these proteins were further shown in both animals and human cells.
Finally, considering the side-effects that accompany significant dietary restrictions e.g. hunger and reduced immune response, a dietary supplement was combined with intermittent fasting.
The combination of the two interventions resulted in an increase in the duration of life that was higher than any of the two alone. In addition, some markers relevant to immunity that were downregulated by dietary restriction were rescued when the dietary supplement was included.
Overall, this work shows an avenue where drugs may be developed to target very specific genes that partake in driving the benefits from dietary restriction, effectively dodging the side-effects and the complexity of undergoing dietary restriction. If the side-effects were to be taken, an alternative shown here is that of combining interventions to reduce these side-effects and even increase the health benefits.
Additional information
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