As you read this, your body is playing host to countless battles. If you’re currently fighting off an infection, this might feel obvious. But, even if you’re well, the two trillion cells that make up your immune system, with a combined weight of over a kilogram (a little over two pounds), are battling against incoming germs, as well as keeping your own cells in check if they misbehave.
Your immune system is critical for preventing everything from infections to cancer, and can even help slow the ageing process. As such, reinforcing your internal army is key to your overall health. But what’s the best way to do this?
Claims in supplement adverts or made by influencers online can be confusing: some will tell you that a given food or pill is ‘immune boosting’, while others suggest that you need to ‘reduce inflammation’.
There’s just one problem – ‘inflammation’ is the scientific term for what happens when your immune system springs into action. So which is it, then?
Should we be seeking ways to increase the power of our immune systems, or searching for things that will turn it down to help keep us in optimal health?
Biology is many things, but it’s never straightforward. Hence the somewhat frustrating answer to that question is ‘it depends’.
But we’re increasingly understanding how our immune systems function, in sickness and in health, and how everything from lifestyle changes to cutting-edge medical treatments could improve our immunity as we age.
So, what are the key lessons we can learn to keep our cellular fighting force in good shape?
Good cop, bad cop
An immune system that fights only when needed is great. But an immune system that’s stuck waging a constant war could be doing more harm than good.
Inflammation is usually good when it’s ‘acute’: the kind that ramps both up and down rapidly when we get an infection or injury. Immune cells rush to the site of the problem, clean things up and then disperse as soon as things are back to normal.
Problematic inflammation is usually ‘chronic’ – a low-level thrum of immune activity, whose chorus often builds to a crescendo with advancing age.
This perpetual paranoia on the part of the immune system doesn’t serve a useful protective function. In fact, it can drive a range of issues as we get older, from cancer to heart disease and dementia.
This is because our immune systems do far more than simply ward off bacteria and viruses. Immune cells also patrol our bodies on the lookout for suspicious cells that might be on the verge of turning into cancer, or damaged ‘senescent’ cells that accumulate as we get older.
As chronic inflammation distracts our immune systems, they get less effective at ferreting out the ‘cells gone rogue’ in our bodies. Even worse, senescent cells can secrete a variety of chemicals that increase chronic inflammation, further reducing the effectiveness with which they’re cleared – a vicious circle that accelerates the ageing process.
That means what we really want to do is help our bodies find a ‘Goldilocks’ zone of immune activity: not too much; not too little; but just right, depending on the situation. Frustratingly, all that means is it’s hard to create a silver bullet.
All is not lost, however: straightforward health advice can help keep your immune system optimally tuned. For example, fat tissue seems to drive chronic inflammation.
Scientists aren’t sure whether it’s the fat cells themselves, or the immune cells that hang around near them that are the causal factor here – but, either way, trying to maintain a healthy weight can be good for your long-term health by dialling down this process.
Similarly, active muscles seem to secrete anti-inflammatory molecules, while static ones drive inflammation, which means moving is a powerful immune optimiser. So exercise is good, but trying to avoid being sedentary throughout the day is also beneficial.
You can try to do this by finding opportunities to stand up and take a few steps every hour, rather than sitting at your desk all day and only going for a walk or swim before or after work.
Secure your perimeter
Some enemies will always find a way in, but there are simple steps you can take to fortify your defences.
While the acute inflammation that accompanies an infection is incredibly important, there is evidence that being ill exerts a cumulative cost on our long-term health.
One paper found that adults who grew up in an era of high childhood mortality (suggesting that they were exposed to a high burden of infectious disease, but were fortunate enough to survive) also had higher mortality at older ages. This implies that the inflammation caused by fighting off infections could increase our risk of diseases as we get older.
One infection that has a particular association with ageing is cytomegalovirus, otherwise (and more pronounceably) known as CMV. Most of us will get CMV at some point in our lives – it’s transmitted through the exchange of bodily fluids, so often transferred between dribbling toddlers or kissing teenagers.
The infection itself is harmless, perhaps even unnoticeable for most people, but the virus sticks around in our bodies for the rest of our lives, occasionally flaring up again in times of stress or reduced immunity.
While flare-ups probably won’t cause any symptoms (it’s very unlikely to be serious unless you’re immunosuppressed) there’s evidence that low-level persistence of CMV can accelerate the ageing of the immune system.
Because it never quite gets eradicated, our immune system becomes increasingly obsessed with CMV, dedicating more and more immune cells to fighting it, crowding out the immune system’s other functions.
A study in California found that people with the highest levels of antibodies against CMV in their blood (implying that their bodies are actively fighting it) were 40 per cent more likely to die over the next decade than those with lower levels.
Sadly, dodging CMV is a big ask. Yet taking general steps to avoid other infections could help slow down the ageing process, as well as help avoid the immediate misery of being ill: get vaccinated (an annual flu vaccine and up-to-date coronavirus vaccines are the most likely regular ones), wash your hands regularly, cook food thoroughly, and consider wearing a mask if you’re going to be somewhere with a particularly high risk of airborne infection.
If you do all the above and still get ill, it’s public-spirited to stay at home when you’re feeling unwell. Not only should your colleagues thank you for helping them avoid the sniffles, but also for slowing down their rate of ageing.
The other, perhaps more surprising, piece of advice is to brush and floss your teeth regularly. Good oral hygiene keeps the unfriendly bacteria in your mouth at bay, and there’s evidence that this can reduce the risk of heart disease and even, maybe, dementia. It’s another piece of the puzzle suggesting that infections – and the inflammation that comes along with them – might accelerate the ageing process more broadly.
Thymus last words
The general consensus is that your thymus is ‘over the hill’ by the time you turn 30. But there are treatments in development that might give this key part of the immune system a new lease of life.
Our immune systems decline gradually with age, but most of you reading this will have already lost most of one major component of it: the thymus.
Located just behind your breastbone and in front of your heart, this organ is the military academy for T cells – a type of immune cell critical to our ability to adaptively respond to different threats, from infection to cancer.
The thymus peaks early: it produces more T cells in your first year of life than in any subsequent year, and sex hormones produced during puberty accelerate a process known as ‘involution’, where productive thymus tissue turns to fat. By the time you’re 30, 75 per cent of your thymus is gone.
Why this happens isn’t fully understood, but it seems to be an evolutionary adaptation. Perhaps, by living in relatively small groups and only meeting other humans and animals within walking distance, prehistoric people had seen most diseases by their teens.
This meant they could rely on immune ‘memory’ cells, rather than needing to produce new ones throughout their lives. In today’s highly connected world, however, entirely new diseases can emerge and spread globally in weeks or months – and it could save millions of lives if our aged immune systems remained flexible enough.
Scientists are therefore working on ways to either slow the thymus’s decline or, ideally, rejuvenate it as we grow older. One option probably best not tried at home is sterilisation. We know that sex hormones are partly responsible for thymic involution in part from lab experiments: the thymuses of mice who have been castrated are maintained until later in life than those of mice left intact.
There’s also tantalising data showing that eunuchs (boys castrated before puberty) live substantially longer than intact men.
But alas, detailed genealogical records of the medieval Korean eunuchs used to ascertain this doesn’t make note of thymus size. Data in female mice and women is harder to come by because removing the ovaries is far more complex than removing the testes.
If that doesn’t appeal, there are other ideas at various stages of development. In the lab, scientists are working on either gene therapy or drugs to reactivate a gene that’s critical for thymic development called FOXN1, or using stem cells to grow new thymuses (outside the body for later transplant or by injecting the cells into the body).
And one approach in early-stage human trials uses a combination of hormones and the diabetes drug metformin to encourage thymuses to regrow in men aged 51–65.
Though these therapies are exciting and could be with us soon, those of us looking to maintain our thymuses in the meantime should consider exercising.
Consider one study of a group of 55 to 80-year-olds who cycled regularly: they were found to have more T cells fresh from the thymus than sedentary people of the same age, but they also had a similar number to healthy 20 to 36-year-olds.
Turn it off & on again
When all else fails, hit ‘restore to factory settings’. If it works for smartphones, could it work for your immune system?
So, if you’ve got an aged immune system that’s riddled with CMV and chronically inflamed after a lifetime of infections, is there anything you can do? The first thing to say is that all the basic health advice you’ve heard a million times before still works – it’s never too late to start exercising or improving your diet.
But if you’re hoping science might have something up its sleeve, you could be in luck: there’s a medical approach on the horizon that could allow us to wipe the slate clean and start again from scratch.
It’s actually a treatment that medics have been using for decades: a bone marrow transplant. The traditional reason to perform one of these is a blood cancer, such as leukaemia. In this instance, your immune cells begin to divide uncontrollably and often the only option is to entirely remove both the immune system and the stem cells in your bone marrow that produce your immune cells.
The usual approach is to use chemotherapy or radiotherapy to kill the stem cells, and then provide a donation of someone else’s stem cells that end up in your bone marrow, settle down and start producing an entirely new immune system for you.
So, given that a bone marrow transplant can act as an immune reboot, potentially ridding the immune system of chronic infections or misconfigurations, could we use the procedure to give all of us a second chance at a fresh, new immune system?
Possibly. Tests on mice are producing tantalising results: the ones that received fresh blood stem cells from young bone marrow live longer and are in better health.
A bone marrow transplant is a major procedure, however, and doctors would be understandably hesitant to try it on healthy people who are merely old enough to potentially benefit from an immune reset.
The good news is that most experiments in mice didn’t involve the riskiest part of this treatment, the chemo- or radiotherapy used to clear out the aged bone marrow before treatment. This means there’s a chance that this much less risky version could work in humans too.
Rally the troops
To win any battle you need to calibrate your forces to the particular adversary you face and ensure they’re all aiming for the correct target.
If a total immune reboot sounds a bit too adventurous for now, there may be an alternative. One paper published in March 2024 found that bone marrow’s youthfulness could be restored by selectively removing stem cells damaged with age using one of the immune system’s own tools: antibodies.
Antibodies are molecules that bind to a very specific target. Some just gum up the workings of their foe, while others act as flags telling the immune system to come and remove it.
So how can we use the immune system’s own tricks to keep us biologically younger? By rebalancing our immune cells.
Bone marrow stem cells (see ‘Turn it off and on again’, above) make immune cells split into broad families: myeloid and lymphoid.
Cells in the lymphoid family make up our ‘adaptive’ immune system, which can adapt to specific threats – think of them as precision-striking special forces. Their ranks include B cells (the ones that make antibodies), and T cells (see ‘Thymus last words', above).
Myeloid cells, by contrast, are rapidly moving infantry. They’re able to target any threat, but with far less specificity – they’re a great first line of defence because they’re much faster acting than adaptive immunity, which takes a few days to get into gear. As we get older, however, an overabundance of these myeloid cells can drive chronic inflammation.
The reason we have more myeloid cells as we get older is because the stem cells in our bone marrow become ‘myeloid-biased’ – they form the wrong ratio of cells, resulting in too many of the first-responder kind and not enough of the more thoughtful, adaptive immune cells. It’s a ‘shoot first, ask questions later’ approach.
Thus, researchers identified antibodies that would stick to aged, myeloid-biased stem cells in the bone marrow, clearing them out of the system and restoring balance to immunity.
When they gave these antibodies to aged mice, it improved their ailing immunity, including their ability to fight off the (pretty poorly named) Friend virus (FV) after being given a vaccine.
Another paper from 2024 used antibodies to clear out an inflammatory molecule called interleukin-11 (IL-11), and mice given it in middle age lived 25-per-cent longer than their peers – that puts these antibodies up there with the best anti-ageing drugs we’ve tried in mice. And, even better, early-stage trials already indicate that they seem to be safe in humans.
All of this hopefully signals a future where it won’t just be the ‘old favourites’ of diet, exercise and avoiding infections that keep our immune systems healthy as we get older.
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