Mucin 55B and its effect on healthy ageing

Abstract

Chronic inflammation is a major symptom of many age-related diseases such as, Alzheimer’s and dementia. This inflammation has been linked to the movement of bacteria from the gut to outside of the lumen into lymphoid tissues and the bloodstream. Understanding the importance of the gut barrier and its integrity is therefore of the upmost importance. Here we use the model organism, Drosophila melanogaster, to investigate how this barrier is regulated.
Mucin genes have long since been known to be a contributing factor to the maintenance of the gut intestinal barrier. We use a drug-inducible UAS-Gal4 system in order to knockdown one of these mucins, mucin 55B. Unpublished data had previously shown a knockdown of this gene extended lifespan and maintained gut intestinal barrier function later into life.
We used AMPs as readouts for the Toll and JNK pathways and found that the mucin 55B knockdown has no effect on this immune response. Further markers were used to find the same result in the insulin pathway. Using antibiotic lifespans we were not able to confirm that the presence of the gut microbiota extended lifespan. We sought to find how mucin 55B was regulated as this could aid in treating late life inflammation in both Drosophila and humans. Here we show that the JNK pathway is likely to regulate the expression of mucin 55B.
This research has broadened the understanding of the impact mucins have on lifespan as well as health span and provide new insight into how approaches can be used to maintain the gut barrier and reduce morbidity.