Smells change us. Inhale the vapours of an apple pie or a bacon sandwich, and your body immediately starts getting ready for an incoming meal. You salivate. You start to produce more digestive enzymes. Your bloodstream courses with insulin, preparing your organs to absorb the nutrients that you’re about to consume.
But smells can have even more profound effects. Two teams of scientists have found that in worms and flies, the scent of pheromones from the opposite sex can speed up an individual’s ageing process and shorten its life. This happens even if no one has any sex.
Just by being around, one worm or fly can control the ageing process in another, at a distance.
While studying the nematode worm Caenorhabditis elegans, Anne Brunet’s team from Stanford University noticed that males seemed to shorten the lives of the opposite sex (hermaphrodites, whose bodies are female but who make both eggs and sperm).
Other scientists had noticed the same effect 17 years earlier, but they assumed that it was due to the “stress of copulation”. But Brunet’s postdoc Travis Maures found that sterile hermaphrodites still suffered in the presence of males… and even in their absence! When he added hermaphrodites to containers that had previously housed males, they still aged more quickly. Their movements slowed, their bodies deteriorated, and their lifespans shortened by some 20 percent.
The males must be secreting some type of pheromone that stays in their environment and curtails the lives of the opposite sex. The team proved this by showing that mutant males which don’t produce pheromones don’t kill their mates early, while mutant hermaphrodites that can’t sense pheromones are immune to the males’ life-shortening powers.
Meanwhile, Scott Pletcher from the University of Michigan found similar patterns in fruit flies. In 2007, his team showed that the mere smell of food can influence the lifespan of flies. Now they’ve found that sex pheromones can do the same.
The problem with fruit flies is that their sperm is toxic and every sexual encounter shortens the lives of females. To work out what the pheromones are doing, the team needed to somehow expose the flies to these smells without actually allowing them to mate. They did it through a clever genetic trick. A single gene called tra determines whether a fly produces male or female pheromones. By switching it on or off, postdocs Christi Gendron and Tsung-Han Kuo engineered male flies that smell like females, and vice versa.
Using these smell-swapped flies, they found that male flies store less fat, become easier to starve, age faster, and die quicker after detecting the scent of female. (The same thing happens to females that smell male pheromones, but to a less dramatic extent.)
“Initially, we thought that the males were just courting a lot or becoming more active, which wouldn’t be that interesting,” says Pletcher. But after carefully watching the flies, his team discounted these explanations. Instead, they showed that the ageing effect is driven by a few taste-sensitive neurons in the flies’ first pair of legs. When they disabled these neurons or just amputated the legs, the males became immune to the female pheromones.
The team also found a way of reversing this life-shortening effect—conjugal visits. If the males were actually allowed to have sex, their lifespans bounced back. That surprised Pletcher, who notes that people have long viewed reproduction and ageing as opposites. “The more energy you put towards reproduction, the less you have remaining to support your health,” he says. “But in this context, reproduction was actually beneficial.”
Why do these pheromones speed up the ageing process? Neither team knows, but both have some ideas. Pletcher speculates that it may be due to the trade-off between sex and longevity. Insulin, for example, is a hormone that’s best known for its role in controlling sugar levels in our blood, but it’s also involved in ageing. “If you reduce insulin signalling, organisms are long-lived but turn off reproduction,” says Pletcher. Pheromones may boost levels of insulin to get flies ready for sex, “and that might lead to enhanced ageing for reasons we don’t understand yet”.
He also suspects that the clash between expectations and experience is important. If we smell food and can’t eat any, the build-up of digestive enzymes can actually cause us harm. Likewise, male flies that smell females but can’t actually mate may suffer the consequences for their unfulfilled expectations. “They make this bet that they’re going to be reproducing soon, and they engage some physiological changes, like producing hormones.” If there’s no sex, these changes are harmful.
Brunet has a different hypothesis. “This is wild speculation,” she says, “but it may be due to sexual conflict.” By shortening the lives of their partners, males could ensure that their offspring aren’t facing competition from their mothers, while also reducing the mating opportunities available to other males. “That’s something we hadn’t considered,” says Pletcher. “It doesn’t entirely fit with our data because when males mate, some of those negative consequences go away, but maybe that means they are battling back?”
These quirky effects are fascinating in their own right, but it’s unclear if they have any relevance to us or to other mammals. “The jury’s out,” says Pletcher, “but I’m as optimistic as I’ve ever been that this would apply to mice, or even humans.” He’s particularly encouraged that both his team and Brunet’s have found similar phenomena in worms and flies—species that have been separated by over 900 million years of evolution. “Historically, genes and pathways of ageing that have been identified in worms and flies have also been relevant to mice.”
Brunet is more circumspect. “We joke that we should open a fragrance company, with fine-print warning labels that say, Caution: this might cause the premature demise of your mate,” she says. More seriously, she notes that it’s not clear what part pheromones play in sexual communication in humans. Mice clearly do use pheromones for this purpose, so the next step would be to see if mice can influence the pace of ageing in the opposite sex, without ever actually mating. “The experiments could be done, but they’re tricky,” she says.
Reference: Gendron, Kuo, Harvanek, Chung, Yew, Dierick & Pletcher. 2013. Drosophila Life Span and Physiology Are Modulated by Sexual Perception and Reward. Science http://dx.doi.org/10.1126/science.1243339
Maures, Booth, Benayoun, Izrayelit, Schroeder & Brunet. 2013. Males Shorten the Life Span of C. elegans Hermaphrodites via Secreted Compounds. Science http://dx.doi.org/10.1126/science.1244160
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