The great fly gender divide

On average, if you're male, your life expectancy is likely to be shorter than if you're female, and some diseases seem to affect one sex more commonly than the other.  So can the humble fly tell us why? Jenny Regan explained to Chris Smith why she thinks it can...

Jenny - In researching aging, something that really sticks out is that females live longer than males.  In addition to this, when we did some manipulations that could extend lifespan, there are some manipulations that extend female lifespan very well but don't do anything for males.  Specifically, the one that we were interested in is putting animals on a diet.  This can really extend the lifespan of females but males derive much less benefit from being on a diet than females do.

Chris - So how did you pursue that?

Jenny - We used the fruit fly (drosophila).  What we actually started out doing was switching sex in various tissues.  To do this we took advantage of something that is particular to drosophila biology, which is that each cell individually specifies it's own sex. So we could harness this particular feature to switch sex just in specific cell types or specific tissues around the fly and we wanted to see if having a female organ in a male fly would be able to let the males get this lifespan extension that the females get in response to diet.

Chris - So what organ did you do this sex switching on?

Jenny - We looked at the liver analogue, we looked in blood, we looked in brain, and finally we looked at the gut and when we feminised the male gut and put these flies on a diet, what we saw was that the males then responded to being on a diet and their lifespan was extended.

Chris - If one studies the natural history of ageing in these flies (males versus females) and you look specifically at the gut, are there clear differences in what happens in the males and what happens in females as they age in that organ?

Jenny - Yes there is, and this is something that we did in parallel.  We started to look at the guts of  ageing males and ageing females and when we started out we expected that we might see males had worse guts than females because males are shorter lived than females but, actually, what we found was that male guts are really well preserved as they age and this is in real contrast to females.  And when we looked at females over ageing, we saw a real spectacular decline.  So we saw wounds appearing in the gut and we saw small tumours appearing in the gut as well.

Chris - Can you explain why, therefore, on the basis of your observations you see this difference between how long males live and how long females live and why calorie restriction makes a difference?

Jenny - When we looked at female guts, females who had been on a diet actually had better guts than females who had been fed a full compliment of food, and so those restricted diet females had fewer small tumours and few wounds in their guts so it looked like they were really better off from being on a diet.  So, we started to understand that perhaps this difference that people observed for the last few decades, might be explained by the fact that the guts respond very differently, i.e. the males don't really get much of a benefit from being on a diet, whereas the females do.

Chris - What is it about the female biology that means that their gut benefits in this way that the males don't?

Jenny - Well the females, they're really egg machines, especially towards the earlier part of their lifespan they're laying hundreds of eggs a day, so it's really important for them to be able to get as much nutrition from food as possible.  And some related studies recently have shown that females can grow their guts spectacularly when they're required to do so by the demands of egg production so it seems that females have more of a reason to have active stem cells in their gut.  It also is true that females, when their guts are challenged by an infection, their guts responds much more than males in the sense that they repair their gut faster or they switch on stem cells to actively divide more than males do and we think this is probably the root of the difference we see in the male.

Chris - It's not that their gut lets them down, it's something else that's making them age and die prematurely compared with the females, and if you sorted out the guts in the females, they would live even longer?

Jenny - Yes, absolutely.  For females, the gut and the deterioration of the gut is really important, but for the males it looks like something else is important and we think that this could be they don't respond as well to microbial challenge.  So this could be something which is more of an issue for males than it is for females.