Modulating mitochondrial dynamics to improve healthy ageing

Ageing is associated with many structural and functional changes in skeletal muscle in a wide variety of species. Age-related muscle atrophy, muscle weakness and reduced aerobic capacity may result in metabolic disorders. In addition, it may also lead to diminished physical performance in animals and humans. Studies have shown that upon ageing the mitochondrial content of cells has been lowered, which may contribute to impaired muscle performance.

In healthy subjects, mitochondrial content is tightly regulated by the mitochondrial flux. The mitochondrial flux comprise complex processes including biogenesis, autophagy as well as fusion and fission of mitochondria.

Mitochondrial Flux

Sirtuins have shown to be important regulators of the mitochondrial flux. Sirtuins are protein deacetylases that can increase the activity of genes known to be important in the mitochondrial flux. Functioning of sirtuin-regulated gene expression is dependent on NAD-levels. NAD levels are lowered upon ageing and this finding might explain the age-related reduced mitochondrial functioning.

We are interested to study if mitochondrial functioning can be restored by bioactive compounds that positively influence the NAD concentrations in cells. Within this project both in vitro as well as in vivo experiments will be conducted. Mitochondrial content and functioning can be measured using a panel of methods, including fluorescence staining of mitochondria, evaluation of mitochondrial respiration, citrate synthase measurements for mitochondrial activity or confocal microscopy. In addition, we use modern molecular techniques including real-time qPCR, whole genome microarrays and siRNA to study effects on mitochondrial processes.

If you want to participate in this research for your thesis or internship, by for example performing rt-qPCR, fluorescence staining and analysis of mitochondrial morphology, cell culture or whole genome microarray analysis, please contact: