A longevity gene in flies works partly through gut bacteria
A gene associated with longer lifespan in fruit flies for decades appears to work partly through the animal’s gut bacteria.
INDY stands for ‘I’m Not Dead Yet’ — a name that reflects the original discovery behind it. Mutations in this gene substantially extend the lifespan of the fruit fly Drosophila melanogaster, and related genes have been found in other organisms, including humans. INDY encodes a transport protein involved in the uptake of certain metabolites in cells, including citrate — an intermediate in energy metabolism. Reducing INDY activity mimics, in some respects, the effects of caloric restriction, the most robust lifespan-extending intervention known.
But how exactly does INDY influence lifespan? Researchers have now identified a new piece of the puzzle: the gut microbiome. Flies with reduced INDY function have a different composition of gut bacteria than flies with normal INDY function. And that microbiome composition appears to contribute to the lifespan extension.
Gut health and aging: a known but complex relationship
In fruit flies, gut function is a particularly decisive factor in aging. The fly’s intestinal system ages relatively quickly, and the state of the gut — how well its barrier function is maintained, what the bacterial composition looks like — correlates strongly with how long the animal lives. That makes the fly a sensitive model for investigating these kinds of connections.
The new results are a first step, the authors themselves acknowledge. The fruit fly microbiome is far simpler than that of mammals, and which specific bacteria or metabolites are responsible for the effect has not yet been established. The direction of causality is also not fully clear: does the microbiome change as a result of INDY suppression, and does that change extend lifespan? Or are there parallel effects? And to what extent are these connections relevant for mammals and humans?
That last question is not easily answered, but the relevance is not merely theoretical. A human homologue of INDY exists, and there have already been attempts to use it as a target for treatments of metabolic disorders. If the microbiome’s role in this pathway also holds in humans — which remains to be shown — it would expand the toolkit of possible longevity interventions in ways that are, at least in principle, accessible.