RUN run run run run THUD run run run run run THUD. This is the steady beat of the Power Tower as it subjects a cohort of athletes to extreme fitness training. Each round starts with a vertical sprint up a smooth wall, before a jolt from the machine sends them tumbling to the bottom again. Hour after hour, hundreds are put through their paces. And wow, do they get results: stronger hearts, faster climbs, greater endurance and a metabolism wired to resist stress. Not bad for a small fly you would usually find haunting bananas or floating face down in your glass of Shiraz.
Fruit flies aren’t the first thing that springs to mind when you think of fitness training, but they are providing a surprising window on the biology of exercise. They aren’t even the strangest invertebrate hitting the gym. That medal goes to a tiny nematode worm called Caenorhabditis elegans whose transparent body allows scientists to see the physical consequences of activity in action.
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But there’s a problem. You can’t just plonk these creatures in front of a workout video and tell them to feel the burn. So how do you get a fly to drop and give you 20 or a worm to run a marathon? Like any good personal trainer, you understand your client’s motivations and craft your workout accordingly. That’s where the Power Tower comes in – along with laser treadmills, electrified swimming pools and other unusual gym equipment. It isn’t just the invertebrates that benefit either. This fiendish research is generating unique insights into how exercise affects human health and ageing.
Thanks to a shared evolutionary history, a fruit fly’s biology has more in common with our own than you might think, including a tendency to be healthier when active. The benefits of working with them are clear. Cheap to keep and quick to reproduce, they have been the focus of more than a century of intensive study by geneticists who have developed an impressive array of tools to probe their bodies. Motivating flies to run is easy, too: they just want to defy gravity. Home for a fruit fly in a lab is a plastic vial with a cotton wool plug stopping the top. Tap a vial so the flies tumble to the bottom and they scurry up to the plug. Keep tapping it and you can get them to do the equivalent of endurance training, which is exactly what Robert Wessells and his team at Wayne State University in Michigan did when they began this research. Trouble was, they grew tired before the flies did. “We just thought, ‘Well, this is pretty tedious’, ” says Wessells. “So we built a little machine that would raise and drop them with a platform so we could put hundreds of vials on there at the same time.” The Power Tower was born.
Now, with four Power Towers on the go, Wessells’s team can put thousands of flies through high-intensity endurance training at once. The regime starts with 1.5 hours of uphill running each day, gradually increasing to 2.5 hours. “It would be like a human who ran at very fast times around their neighbourhood for 5 to 10 hours a week,” says Wessells. The flies’ physiological responses are similar too – at least, they are for males. It turns out that females don’t get as much benefit from training. This, the researchers realised, might be a clue to one mystery of human exercise: why some people get a bigger metabolic pay-off than others.
One promising lead is octopamine, a neurotransmitter that male flies produce more of during exercise than females. Wessells and his team found that artificially increasing the levels of octopamine in sedentary flies like those produced by exercise. Humans have a similar molecule, called noradrenaline, and the researchers have just completed a preliminary study using virtual-reality exercise simulations to try to fool volunteers’ brains into producing it. Results were mixed, with only a few people responding to the treatment. “But it does seem like it should be possible to do basically what we did in the fly,” says Wessells.
Octopamine helps explain one puzzle: why tissues other than the muscles being exercised also experience metabolic benefits. Another clue comes from , proteins that humans and other animals produce when under stress. Wessells and his colleagues have shown that flies need to produce a sestrin in their muscles to respond to exercise, and that it works by altering the activity of molecules that control cellular metabolism. Tissues other than muscles also seem to benefit from this sestrin activity, says Wessells, who is now trying to find out why.
The Power Tower was groundbreaking, but it can only get flies to do intensive training. To measure the effects of more gentle exercise, Nicole Riddle and Louis Patrick Watanabe at the University of Alabama at Birmingham have come up with a fruit-fly treadmill that is a dead ringer for a rotisserie – with lasers.
“How do you get a fly to drop and give you 20 or a worm to run a marathon?”
Their machine, the , is based on another contraption called the developed by Laura Reed at the University of Alabama and her colleagues. The TreadWheel consists of rotating arms to which the researchers clip vials of flies. As the arms turn, they gradually tip the vials end over end, so the direction of “up” is constantly changing. This encourages the flies to jog to keep up – or they can have a sit down if they aren’t really into running. “[Some flies will] run around and do the whole thing for 2 hours,” says Riddle. “Then there are other flies that will do it for 10 minutes and go like, ‘Well, I’m done. I don’t need to do this any more’. ” She confesses to sharing this lack of enthusiasm for strenuous exercise. “The part that always surprises me is they really aren’t that different from us,” she says.
Riddle and her team’s innovation was adding a monitor with laser beams that lets a computer quantify overall fly activity in the tube by counting how many times the insects cross the beams as the machine rotates. This allowed them to study large numbers of flies. They then scanned the genomes of 161 genetically distinct strains for gene variants linked with an individual’s inclination to exercise and response to activity. Riddle and her team found , many not associated with exercise before. “I think there are definitely things we can learn from the flies that then, hopefully, will translate to something that will work for people,” says Riddle.
Swim club
Worms could also teach us a thing or two, especially when it comes to exercise and ageing. C. elegans nematodes live for just three weeks (about half the lifespan of fruit flies), so it is easy to see the effects that exercise has on them over their lifetime. To do this, Monica Driscoll at Rutgers University in New Jersey and her colleagues have been chucking worms in at the deep end. , a quirk that Driscoll’s team tried to exploit to get them to swim laps in a fluid-filled chamber. Unfortunately, the researchers struggled to find the right balance between no laps and fried worms. “So then we switched to: just throw them in the pool,” says Driscoll.
“Worms push past tiny, flexible pillars and crawl out of gel as tests of strength”
With no charge to chase, the worms wriggle around, essentially treading water. Those that do this for 90 minutes two or three times a day for the first few days of their lives see marked benefits, including faster crawling and healthier muscles. They also maintain a , and being active has a big impact on their little brains. “The animals learn better,” says Driscoll. Worms that are genetically engineered to produce the faulty proteins linked with human neurodegenerative conditions such as Alzheimer’s disease have neurons that stay healthier for longer if the animals have exercised. This chimes with findings that exercise helps people reduce their risk of getting dementia as they age. The big question is what molecules and mechanisms underlie this protective effect. “We’re hoping to use the awesome power of C. elegans genetics to understand what is particularly important,” says Driscoll.
Another intriguing discovery – again mirroring what has been seen in humans – is that worms that exercise when they are young but then stop retain the benefits into middle age. The biology behind this isn’t well understood. One idea is that exposure to low levels of stress – the kind induced by exercise – sets the body’s priorities when it comes to preventing and repairing damage, an effect biologists call hormesis. “The idea is that a moderate or small stress, early, ups your defences,” says Driscoll. “There’s a saying: ‘What doesn’t kill you makes you stronger’.”
Her team is now working with microfluidics engineers to design chips that could house the worms and then automatically push them into the pool, without human intervention. Cameras and other machines would record data on each worm over the entire course of its life. As well as making things easier for the scientists, this kind of set-up would allow them to study differences between individual worms.
So far, worm and fly research has focused on the metabolic effects of exercise, rather than building muscle or losing weight. That could change with new exercise regimes, though. Driscoll gets her worms to push past tiny, flexible pillars or to test how strong their muscles are. That isn’t so different from pumping iron, although strength training isn’t on Driscoll’s radar for now. Wessells, meanwhile, is looking into it: he is investigating the possibility of gluing tiny metal weights to his flies’ backs, as other scientists studying fly gait have done. Taking a leaf out of NASA’s book, he has also tried putting fruit flies into a centrifuge, although he describes the results of his first attempts as “a little bit chaotic”.
Still, given the huge potential of exercise research with flies and worms and the determined ingenuity of the scientists who study them, it surely won’t be long before a new range of workout equipment arrives at a creepy-crawly gym near you.
