Gender divide: why females outlive males

On average, males tend to live less long than females, and some diseases affect one sex more commonly than the other.  So can a fly tell us why? Jenny Regan explained to Chris Smith why she thinks it can...

Jenny - In researching aging and looking at lifespan of various species, 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 ones 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? What did you actually do to try and find out why there's that sex difference?

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 which is particular to Drosophila biology, which is that each cell individually specifies its own sex. Whereas in mammals, you would have circulating sex hormones like oestrogen or testosterone which tells different tissues to develop to a particular gender. What you find in fruit flies is each cell individually counts how many X chromosomes it has and specifies gender that way. So, we could harness this particular feature to switch sex just in specific cell types or specific tissues around the fly. And then we subjected them to a diet and we wanted to see if having a female organ in a male fly would be able to let the males get this kind of 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 the brain, and finally, we looked at the gut. When we feminised the male gut and then 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 difference between what happens in the males and then what happens in the 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. When we started out, we expected that we might see males had worse guts than females because males are shorter lived than females. Actually, what we found was that male guts are really well-preserved as they age. This is in real contrast to females. 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 these difference between how long males live and how long females lives, and why calorie restriction makes a difference?

Jenny - Yes, so this is what came out of the next step of the study 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 complement food. And so, those respected diet females had fewer small tumours and fewer wounds in their guts. So it looked like they were better off from being on a diet. So we started to understand that perhaps this difference that people observed for the last few decades in lifespan responds to diet 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 - The females, they're really egg machines especially towards the earlier part of their lifespan. They're laying hundreds of layers 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 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, so by an infection, their guts respond much more than males do in the sense that they repair their guts faster or they switch on stem cells to actively divide more than males do. We think that this is probably the route of the difference that we see in the male.

Chris - So something else is holding back the males?  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. 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.