Prof Petros Ligoxygakis
Professor Petros Ligoxygakis
Associate Professor of Genetics
Department of Biochemistry
University of Oxford
Host - Professor Robin Williams
Is immunity costly for the ageing brain? Using drosophila to find out
The term inflammaging denotes an up regulation of the inflammatory responses that occur with age, resulting in a low grade chronic systemic inflammation. It is characterised by raised levels of pro-inflammatory cytokines all of which have been shown to be associated with age-related brain neurodegenerative disease. The "executors" in this immune to brain pathway are the microglia. In the aged brain, the microglia have a primed phenotype as a consequence of changes in their local micro environment. Systemic inflammation impacts on these primed microglia and switches them from benign to aggressive types with the enhanced synthesis of pro-inflammatory mediators.However, little is known about the genetic background and molecular mechanism that predisposes individuals to chronic inflammation and the connection to neurodegeneration.
To this end, our Lab is studying the cost of immunity in the brain. Normal flies in germ free conditions live less and have brain degeneration in old age compared to flies that have their immune system knocked out. Conversely, fruit flies with chronic activation of immunity in the absence of infection show a dramatic reduction in lifespan, severe brain neurodegeneration and locomotion defects. All these phenotypes are rescued when we suppress the immune system in glia cells. I will discuss these results in relation to what is known in mammals/humans.