Smells of other females make mice live longer

Exposing young mice to the smells of other mice can affect their rate of sexual maturation. And in an extraordinary set of experiments, as he explains to Chris Smith, Mike Garratt, who’s at the University of Otago, has found that it also affects how long the animals live…

Mike - It's been known for a long time that in rodents, if you expose a female mouse to smells of a male, she will become sexually mature very fast, or faster. Probably because she perceives that there's mates in her environment. Similarly, if you expose a female mouse to smells from other females, she will slow down her rate of sexual development, presumably because there might be other competitors in her environment. So we are really interested in this idea of smells of other individuals that we know influences sexual development and whether that could influence the aging process also.

Chris - Do we know how those smells are interpreted in the body in, in order to have those effects?

Mike - We know partly they are detected by parts of the olfactory system in the brain, and those smells are capable of altering the hormones that are released from the brain that influence sexual development.

Chris - And so how did you then take that, the step further that you're outlining and ask, does this affect how long an animal will live?

Mike - Well, ultimately, if you want to answer that question, you have to do an experiment and actually study the lifespan of an animal. We set up an experiment where we took male and female mice. We expose them to either the odours of other males or other females early in their development. We checked that this changed their rate of sexual maturity, and then basically we left those animals and we studied how long they lived. The outcome was that female mice who are exposed to female odours show a slowdown in their sexual maturity, but they actually live longer. We found that females who are exposed to males become sexually mature earlier, but this doesn't seem to affect their survival, and we didn't see any effects of these odour cues on male survival. So it really seems to be that if you take female mice and you expose them to female odours, which we know slows down their sexual maturity, this does something to their physiology, which means that they live longer.

Chris - How specific is this to mice? If I took the smell of a female cat, great friend of a mouse <laugh>, and I, and I exposed the mice to it, is there something about females in general that smell a certain way or has it got to be a mouse?

Mike - Yeah, it's, it's a really good question and I would suggest probably it wouldn't affect the survival of a female mouse because we don't know what the pheromones are that are driving this process, but it's probably something specific to mice. However, there are some pheromonal cues that are found across species. So sometimes male sense can be stressful and you can take a male mouse and expose a female mouse or a male mouse and expose them to the center of a male from many different mammal species, and that will cause a stress response.

Chris - When this translates into a difference in life expectancy of, of a mouse exposed in this way, how big is that difference?

Mike - It was about a 9% difference in survival. But that's actually quite large. So I think it was sort of maybe 80 days difference. And the delay in sexual maturity that we see with exposure to female odours is only about five to 10 days. So actually you're getting a much bigger change in survival than you are in sexual maturity. A sort of eight 9% difference in survival in a mouse is equivalent to five to seven or eight years in a human.

Chris - Do you know why this is happening? Because it does seem to be a consistent thing that there's something to do with sexual maturity because we know that dogs that have been castrated tend to live longer than uncastrated animals, even humans that have been castrated - eunuchs - allegedly live longer. So do you have any insights as to why this effect is happening?

Mike - No, I mean, and that's I think gonna be a really big question in general over the next five to 10 years. So you're exactly right. There is this consistent effect of if you withhold reproductive investment, it can extend lifespan. And that's been shown in various different species. If you take away the gonads from an animal, so you completely stop them from being able to reproduce, they live longer. And our and our research shows that actually even if you just sort of tweak the age at which they become sexually mature it influences their survival. These hormones that are produced during sexual maturity have effects on cells that influence the signaling processes that regulate growth, either the growth of cells or the growth of the whole body. And we know that some of these signaling processes themselves can directly influence the lifespan of an animal. So there are certain signaling molecules within cells that detect hormones and regulate cell growth. If you inhibit those with specific drugs, you can also make animals live longer. Like you can make a mouse live 20% longer by treating it with a drug that will impinge on some of those signaling processes. So I suspect there's a connection between the hormones that regulate reproduction and those pathways within the body that influence growth related processes and also aging.

Chris - Did you look at what the mice died of when they either did or didn't live longer to see if there was an excess of, of certain pathologies in those that didn't live as long and those that did?

Mike - No, we, we didn't do that within this study. I kind of wish we had, it's very expensive to do that kind of pathological analysis. We did test the physical function of our mice later in life just to see if there are any changes in their strength or their running ability, and we didn't see any overt differences. It is possible that, you know, you may be seeing changes in pathology in a particular organ or maybe an increased or decreased rate of a certain cancer. That's something we, we haven't explored, but that is something we are planning to do in future experiments where we're looking at the effects of social cues on aging in mice.

Chris - And why just the females?

Mike - Yeah, I don't know. In female mice, age at section maturity is quite flexible. And that's quite easy to study in a female mouse, but it's much harder to study in a male mouse. So we don't really know whether age at sexual maturity is as flexible in males as it is in females. So it's possible that males have just evolved to be less flexible in their kind of life history strategies effectively.