While exercise is important for a long and healthy life, ultramarathons may accelerate the ageing of cells in our blood. Athletes who ran 170 kilometres over mountainous terrain accumulated more age-related damage to their red blood cells than those who completed a shorter distance.

Long-distance running has been linked to health issues before, such as temporary suppression of the immune system and anaemia. But we only now have an understanding of what it does to red blood cells 鈥� which transport oxygen around the body 鈥� particularly when done outside on mountainous terrain.

at the University of Colorado Anschutz and and his colleagues analysed blood samples from 11 adults aged 36, on average, within a few hours before and after they ran a trail 40-kilometre race. They did the same for a separate group of 12 people of around the same age who competed in a 170-kilometre ultramarathon over similar terrain.

The researchers found that competing in either race seemed to cause the runners鈥� red blood cells to accumulate more damage from molecules known as reactive oxygen species, which are produced at higher levels when these cells need to deliver more oxygen around the body.

But such damage, which naturally accumulates as red blood cells age, was substantially higher in the ultramarathon runners. 鈥淎necdotally, the blood after an ultramarathon looks like the blood of somebody who鈥檚 just been hit by a car,鈥� says D鈥橝lessandro. 鈥淭he red blood cells accumulate damage and become more aged.鈥�

Running the ultramarathon, but not the shorter race, also seemed to cause their red blood cells to shift more rapidly from a disc shape to a more spherical one, which is typically seen when they age. The disc shape allows them to bend and squeeze through tiny blood vessels in the spleen, where old red blood cells are destroyed. 鈥淭his spherical shape means they get stuck in the spleen and eaten up by immune cells,鈥� says team member , also at University of Colorado Anschutz.

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This damage is probably due to exercise increasing inflammation and particularly strenuous activity pushing red blood cells more forcefully around the body, he says.

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What鈥檚 more, only the ultramarathon runners experienced a roughly 10 per cent drop in their red blood cell numbers after the race, but this isn鈥檛 necessarily a problem for their health. This change is too small to cause anaemia and the body can probably rapidly recover from it, says Nemkov.

The researchers are now studying the red blood cells of ultramarathon runners a day after they have completed a race, in order to better understand how long these effects last. They also want future work to examine whether these changes affect runners鈥� performance. 鈥淭his could just be what the damage signals look like to make the body more resilient to endurance running, or it could have a negative impact,鈥� says Nemkov.

Researchers have identified neurons in mice that help build endurance after running. They suspect that similar cells exist in people, which could be targeted with drugs or other therapies to amplify the effects of exercise.

We have known for decades that the brain changes with physical activity. Yet scientists widely believed these effects are distinct from those occurring elsewhere in the body, like muscles growing stronger, says at the University of Pennsylvania. The latest findings suggest otherwise 鈥� the brain changes 鈥渁re what coordinates all that other stuff鈥�, he says.

To better understand how exercise influences the brain, Betley and his colleagues monitored neuronal activity in mice before, during and after treadmill exercise. They zeroed in on cells in the ventromedial hypothalamus, as previous research has shown that hinders fitness improvements in rodents. The same is probably true in people, because the region鈥檚 structure and function tends to be consistent across mammals, says Betley.

The team found that after the mice had run, activity increased in a group of neurons with a receptor called SF1, which . What鈥檚 more, the proportion of these cells activated by exercise grew with each additional day of running. By day eight, running activated about 53 per cent of the neurons compared with less than 32 per cent on day one. 鈥淪o, just like your muscles build when you鈥檙e exercising them, your brain activity builds,鈥� says Betley.

Next, the researchers used optogenetics 鈥� a technique that activates or inhibits neuronal activity with light 鈥� to turn off these neurons in a separate group of mice. The animals trained on a treadmill five days a week for three weeks. After each session, the neurons were inhibited for one hour. At the end of each week, the mice completed an endurance test, running to the point of exhaustion.

Over the course of the experiment, the mice increased the distance they ran on these tests by about 400 metres, on average, but this was roughly half the improvement seen in another group of mice whose neurons were left intact.

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It isn鈥檛 clear what the role of these neurons is, but it may relate to fuel utilisation, says team member , also at the University of Pennsylvania. During endurance activities, the body fuels itself with fat, as carbohydrate stores deplete more quickly. But inhibiting these neurons in the mice led them to 鈥渟tart using carbs a lot earlier on in the run鈥�, says Kindel. 鈥淭hen, they are kind of out of fuel.鈥� The team found that inhibiting these neurons prevents the release of a protein called PGC-1 alpha in muscles, which helps cells use fuel more efficiently. These neurons also release a substance that increases blood sugar and replenishes energy stores, aiding muscle recovery.

Optogenetics requires invasive brain surgery, so isn鈥檛 feasible in people. But it may be possible to develop other interventions that could act on these neurons, says Betley. 鈥淚 really do think that if we could find a way 鈥� a salt, a supplement 鈥� to activate these neurons, you can increase endurance,鈥� says Betley.

When the researchers repeated the experiment, boosting rather than inhibiting activity in these neurons, they found just that: the mice developed Herculean endurance, running more than double the distance of control mice.

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A similar intervention could particularly benefit people who have difficulty exercising, such as older adults or those who have had a stroke, says Betley.

But there are many hurdles in the way. For one, we don鈥檛 know for sure if these findings translate to people. There is also the question of potential side effects, says at the University of Florida. These neurons seem to regulate energy uptake in muscles, so stimulating them too much could cause a dangerous drop in blood sugar, he says.

Even if we can safely activate these neurons in people, it won鈥檛 be a silver bullet for good health, says Betley. 鈥淎ll sorts of great things happen when you exercise 鈥� you鈥檙e less depressed, less anxious. There are cognitive improvements, cardiovascular improvements, muscle improvements,鈥� he says. 鈥淚 don鈥檛 think that activating [these] neurons is necessarily going to be the bottleneck through which all of those good things happen.鈥�

Exercise is tremendously beneficial for our health in many ways, but it鈥檚 not that effective when it comes to losing weight 鈥� and now we have the best evidence yet explaining why this is.

People who start to exercise more burn extra calories. Yet they don鈥檛 lose nearly as much as weight based on the extra calories burned. Now, an analysis of 14 trials in people has revealed that our bodies compensate by burning less energy for other things.

What鈥檚 more, this compensation effect is greater if people eat less as well as exercising more 鈥� and can completely cancel out the extra energy spent exercising. In other words, while eating less will result in weight loss, exercising while dieting may not result in any additional weight loss.

鈥淭he real killer here is that if you pair exercise with diet, your body goes, 鈥榝ine, well, then I鈥檓 going to compensate more鈥�,鈥� says at Duke University in North Carolina. 鈥淚t鈥檚 still good for you, just not for weight loss.鈥�

When Pontzer , he was amazed to find that despite their physically active lives, they used no more energy overall than people who sit at a desk all day. This discovery led Pontzer to propose, in 2015, that our bodies have evolved to limit how much energy we burn, and compensate for greater physical activity by saving energy in other ways.

There are studies that back the idea, but not everyone in the field is convinced. Now, Pontzer and , also at Duke University, have identified studies done for other reasons whose findings can be analysed for evidence of compensation. These studies shouldn鈥檛 be biased in relation to whether compensation occurs, says Pontzer. 鈥淭hey had no dog in the fight when the data were collected.鈥�

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In particular, the pair looked at 14 trials involving around 450 people altogether (the numbers are small because monitoring overall energy expenditure requires using specialised, expensive methods). On average, Pontzer and Trexler found that people鈥檚 total energy expenditure increased by just a third of what would be expected based on the increase in exercise.

For instance, Pontzer says, suppose people did enough exercise to burn an extra 200 kilocalories a day. Their total energy expenditure, in these studies, only increased by about 60 kilocalories.

But there was a lot of variation within this. For people who continued eating as normal, total energy expenditure increased, on average, by half of what would be expected. But for those who ate less at the same time as exercising more, total energy expenditure often did not go up. 鈥淭hey鈥檙e doing that 200 kilocalories a day of exercise, but it鈥檚 not showing up at all,鈥� says Pontzer.

The type of exercise mattered, too. Compensation occurred only with aerobic exercises, such as running. With weightlifting or resistance training, energy use went up by more than expected. For instance, the total energy expenditure of people who expended an extra 200 kilocalories lifting weights went up by 250 kilocalories a day.

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It鈥檚 hard to measure how much energy people use lifting weights, Pontzer says, so these findings need to be treated with caution. But he speculates that weightlifters might be burning extra energy to repair and build muscle.

Pontzer had previously thought the type of exercise didn鈥檛 matter. 鈥淚t鈥檚 really a surprise to me,鈥� he says. 鈥淚 think it鈥檚 exciting and points to something that we hadn鈥檛 known before.鈥� However, people who did weightlifting in these studies gained muscle and hardly lost any fat, Pontzer says. 鈥淪o it鈥檚 still not a good way to lose weight.鈥�

So, why doesn鈥檛 our total energy use go up by as much as would be expected when we do more aerobic exercise? The analysis suggests that our bodies compensate by reducing the amount of energy dedicated to all the background tasks it does. The resting metabolic rate, particularly during sleep, may fall in response to more aerobic exercise.

鈥淲e鈥檙e changing what our different organ systems are doing [after exercising],鈥� says Pontzer. 鈥淎nd if we can figure out exactly what鈥檚 changing, we鈥檙e going to understand a lot more about how exercise affects our body [and] why some people seem to benefit from exercise more than others.鈥�

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While Pontzer sees the findings as very clear evidence of compensation, others are still not convinced. at the University of Bath in the UK points to a concluding that aerobic respiration does not alter the resting metabolic rate.

There are also some key analysed, says , also at the University of Bath. For instance, the extra exercise people were asked to do might have , such as gardening. This could explain why people鈥檚 energy usage didn鈥檛 go up by as much as expected, Gonzalez says.

But Pontzer says this can be ruled out in some of the studies. Compensation has also been seen in animal research, backing the human results. Nonetheless, Thompson and Gonzalez think more rigorous studies are still needed. 鈥淲e really need carefully designed randomised controlled trials in humans,鈥� says Thompson.