Increasing ADAR activity in Drosophila intestinal stem cells extended the flies' lifespan

Increasing ADAR activity in Drosophila intestinal stem cells extended the flies' lifespan

On July 28, Science Signaling published a study describing how the Drosophila intestine switches between repair after injury and routine tissue renewal. The authors increased dADAR activity in the intestinal stem cells of old flies. Their intestines functioned better, and the flies lived longer.

The intestine continually renews its inner lining. In undamaged tissue, stem cells rarely divide. After injury, they divide rapidly to replace lost cells. This pattern breaks down in old flies: the cells divide too often, the intestine develops abnormal growth, and its ability to maintain itself declines.

The authors traced this defect to ADAR, an enzyme that edits RNA, the molecule used to make proteins. dADAR activity was lower in the intestinal stem cells of old flies. The enzyme edits the RNA encoding the Pumilio protein. Edited Pumilio suppresses the production of MAPK components, which form a signaling pathway that instructs the cell to divide.

The pathway works as follows: dADAR edits Pumilio RNA, Pumilio restrains MAPK, and the stem cell remains quiescent. When the researchers disabled dADAR (the fly version of the enzyme) in cells from young flies, the cells began to proliferate excessively, and the intestine aged more rapidly.

After intestinal injury in flies, dADAR levels fell, allowing the cells to begin dividing. In an undamaged aging intestine, high dADAR levels prevented continuous cell division. The same regulatory component allows the intestine to repair itself quickly after injury and keeps its cells quiescent between injuries.

Increasing dADAR activity in the stem cells of old flies reduced age-related intestinal dysfunction and extended lifespan. In this Drosophila study, lifespan changed with the intestine's ability to switch its stem cells from repair mode to quiescence at the appropriate time.