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Gentle regular exercise could reduce the risk of liver cancer in mice

by Alex Lathbridge | Analysis

15 February 2021

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Around 17 new cases of liver cancer are diagnosed every day in the UK.

There are many risk factors associated with developing liver cancer. Two of these are age and damage to the liver, with both affecting our immune system.

When it comes to staying healthy, exercise is often suggested as one of the tools that people of all ages can use to keep themselves – and their immune systems – in good shape. Though exercise isn’t a cure for liver cancer or other liver diseases, could there be some way that exercise could help alleviate some of the damage caused to the organ?

Professor Derek Mann and Dr Caroline Wilson from the Newcastle University Centre for Cancer and a team of Cancer Research UK-funded scientists have been looking into just that.  They’ve found some promising results – in mice, at least.

Inflamm-aging

As we age, two things begin to happen to immune system. Firstly, it slowly starts to struggle making new white blood cells to help defend the body. Secondly, it undergoes something known as “inflamm-aging”, where the brakes on your immune system have slowly worn out and are less likely to prevent chronic inflammation.

And while inflammation is a powerful weapon against bacteria, toxins and other threats, a prolonged state of inflammation can cause tissue damage. It’s been known for over a century that inflammation plays a major role in cancer across the globe.

“When you’re young, the brakes on your immune system are excellent at preventing it running away, but those brake pads get worn away as you age,” says Mann.  This can have consequences for the body, as the team discovered in a previous study. They found that mice with chronic inflammation showed increased signs of aging due to it, including thinner skin and less dexterity. More work also showed that these mice are more susceptible to developing liver cancer caused by liver damage.

“We wanted to ask if exercise, crucially exercise that someone who might be frailer could achieve, could help throw that immune decline into reverse, and reduce the risk of liver tumours developing,” says Mann. So the researchers looked at a particular type of mice that develop chronic inflammation as they age. They split these older mice into two groups: 16 exercisers and 13 sedentary mice.

You can’t exactly get mice to lift weights and this was gentle exercise – not over the top. We’re not doing Usain Bolt or Mo Farah.

The mice in the first group were put on a moderate exercise regime: a 30 minute jog on a mouse treadmill, helped along by small puffs of air. They’d then be weighed and have their bodies checked over at the same time as the mice in the sedentary group.

After 3 months, the team found that the mice in the exercise group had changed more than they expected. Their liver inflammation had reduced and had less fat, a good sign as fat in the liver is associated with liver damage.  As well as this, there were improvements seen in other parts of the body.

From previous work with these mice, the researchers expected about half of them to develop a tumour in their liver. In the sedentary group, 5 out of the 13 mice developed these tumours. But out of the 16 mice who underwent this exercise regime for 3 months, only 1 developed was found to have a tumour growing.

But why?

So at this point, the team could say that – for these specific type of mice – increased exercise resulted in lower inflammation. But why was this the case?

It turns out, the changes could be traced back to inside the mice’s cells themselves – or rather, to their cells’ biochemical pathways.

The researchers compared the processes going on inside the cells – the biochemical reactions involved in the production and breakdown of molecules that control a cell’s function. What they found was that – in the mice that exercised – certain molecules were being made in their bodies in much higher quantities than in the non-exercise group.

It’s thought that by switching on this increased production, these molecules affect other key processes in the liver and the immune system, preventing damage to the liver, as well as promoting improvements in other organs like the lungs and stomach and decreasing fat build up in the liver.

Though the team have shown the effect of exercise on this intricate process inside these mice, they can’t yet say for certain that a specific amount of exercise reduces liver tumour risk by a set amount. This is a much more complicated question, and these results have opened the scientists up to an exciting new area of research.

Looking forward, they already have plans to see if some of the cellular results translate to similar findings in humans with liver cancer. They also want to find out if a tailored exercise regime could help improve the effectiveness of someone’s main cancer treatment.

Alex