Carbon Dioxide and Lifespan in Drosophila

My first post to this blog began with a fascinating study by Scott Pletcher that found odor from yeast can accelerate the ageing of dietary restricted Drosophila.  His group recently published another study that adds to our understanding (1), which I summarize below.

The investigators chose carbon dioxide (CO2) to study because of its known role in behavioral signaling in insects, so it was speculated that it may mediate the perception of food availability; fruit produce it as well as live yeast.  It also seems to be released as a pheromone to signal avoidance in stressed flies.

They used a CO2 receptor knockout (Gr63a) Drosophila model.  Interestingly, only females lived approximately 30% longer than controls, and this increase was primarily because of a reduction in baseline mortality.

Because the Gr63a mutation is recessive, they confirmed that flies with 1 mutant allele and 1 wild-type have a lifespan similar to wild-type flies; only homozygous mutant flies experience a lifespan extension.

Another experiment allowed for transgenic rescue of Gr63a mRNA expression even when Gr63a was knocked out to confirm that the longevity extension was due to Gr63a loss of function per se.  The transgenic expression reduced lifespan to wild-type levels, and overexpression of Gr63a did not further alter longevity.

An additional experiment found that a partial loss of ab1C neuronal function increased lifespan comparable to the homozygous mutant Gr63a experiments, and this again was because of a reduction in initial mortality.

To further elucidate relationships between fat metabolism, reproduction, stress, and ageing, triglyceride levels and fat deposition were measured.  In Gr63a mutants, both were increased relative to wild-types, heterozygous mutants, or transgenic rescue flies, but they did not have an increased resistance to starvation despite these increases.

Interestingly, experiments examining reproduction by measuring egg production found that Gr63a homozyous mutants produced more eggs, suggesting reproductive ability does not come at a cost to longevity, contrary to other longevity increasing manipulations.

The mutants also had an increased resistance to paraquat induced oxidative stress.

Sleep-wake cycles were generally not altered in the knockouts.

Then, the authors investigated if the mechanism for lifespan extension in Gr63a mutants is independent of those affected by dietary restriction.  Interestingly, lifespan was further extended in Gr63a mutants subjected to dietary restriction, by a similar magnitude to control flies also subjected to dietary restriction.  This suggests that Gr63a influences longevity independently of dietary restriction.

Finally, subsequent experiments found that live yeast odor but not other odorants that are indicative of a nutritious food source (mango, apple cider vinegar) reduced longevity of dietary restricted Drosophila.  Gr63a mutants were less able to locate live yeast, and when wild-type flies were give access to live or dead yeast, they preferred the live, suggesting that CO2 is important for detection of the food source.  Also, killed yeast did not alter lifespan of any group of flies.  Yeast odorants did not impact the longevity of Gr63a mutants, but in Or83b mutants that have a loss of olfaction detection but still can sense CO2 did have reduced lifespans, as found in the previous study.

Conclusions

All of these experiments together suggest that specifically CO2 detection, and not necessarily a broad reduction in olfaction influences longevity in Drosophila.  Though there are some differences in results between these experiments and the previous, suggesting there are at least 2 distinct pathways in which sensory signaling can influence ageing.  The authors suggest that this is because CO2 provides information about nutrient availability, and has an additional role in behavioral responses to food sources.  The sex-specific (female) influence has been noted in other areas of longevity research, but remains to be studied in detail.  The authors speculate that it may be because of physiological nutrient requirements for reproductive processes.  They also highlight the intriguing possibility of human manipulation of sensory systems because we may have genetic conservations that may influence healthspan through similar mechanisms.

Reference

1. Poon PC, Kuo TH, Linford NJ, Roman G, & Pletcher SD (2010). Carbon dioxide sensing modulates lifespan and physiology in Drosophila. PLoS biology, 8 (4) PMID: 20422037