There has never been a more important time to keep your immune system fit and healthy.
As we age the immune system gets weaker – which is a key reason why those over the age of 70 are most at risk from viruses and disease. What’s now becoming clear is that when it comes to immune health, age is just a number.
Why?
Because some people have an immune system that is effectively significantly older or younger than they are.
In fact, Shai Shen-Orr, an immunologist at the Technion-Israel Institute of Technology says that “some 60-year-olds have the immune system of a 40-year-old, some are more like an 80-year-old.”
As anyone who has studied immunology will tell you, the immune system is immensely intricate. “It is the second most complicated system in your body after your brain,” says Shen-Orr.
It consists of hundreds of cell types and signalling molecules controlled by some 8000 genes, interacting in a network of near-infinite complexity. Happily, you don’t need to know all of its intricacies to take advantage of the latest developments in immunology – although a little knowledge can help.
If you are younger than 60, in good health and don’t have too many bad habits, then your immune system is probably functioning well enough to keep you safe from almost any infectious disease, including coronavirus. The bad news is that as we age, our immune systems gradually deteriorate too. This “immunosenescence” starts to affect people’s health at about 60, says Janet Lord at the University of Birmingham, UK.
To many, immunosenescence may sound like a far-off threat, but it is something that should concern us all. The decline starts surprisingly early in life, during puberty, and can be accelerated by all kinds of lifestyle.
People who smoke or who are obese are particularly likely to have an immune system that is older than their chronological years.
Being sedentary is another risk factor.
This has led to a new concept called immune age. It is similar to biological age, which uses chemical tags progressively added to genes throughout life to measure how far down the trajectory of ageing somebody has travelled, regardless of the number of years on the clock.
Biological age and chronological age are usually quite tightly coupled but can diverge by as much as 20 years either way.
And unlike chronological age, biological age can go down as well as up, usually because of deliberate lifestyle changes.
Both, it turns out, are also true of immunological age.
This way of thinking about the immune system has many uses. Knowing our immune age could help doctors judge how susceptible we are likely to be to illness.
It might also help us all to maintain and strengthen our immune system.
For instance, it could be used to validate supposed immune-boosting strategies. Does it affect immune age? If not, think twice.
Until very recently, it was impossible to measure immune age. But last year, a team led by Shen-Orr and Mark Davis of Stanford University in California revealed a way to do it.
Using a “multi omics” approach – looking at a person’s genome, immune system, and protein function – the researchers audited the immune systems of 135 people in two age brackets, 20 to 31 and 60 to 96. They then repeated the measurements several times over nine years.
What they discovered was that human immune systems follow a predictable trajectory.
“We can give you a number which says where you are along this trajectory. That is your immune age,” says Shen-Orr. “And it is a very good predictor of all-cause mortality.”
Immune age measurement is still new and there is no commercially available test, although the team is working on one. For now, probably the best way to gauge your immune age is to get your biological age tested, because the two seem to be roughly correlated.
Regardless, you don’t need to know your immune age to take steps to start lowering it.
And it turns out that many of the emerging anti-ageing drugs and strategies do their stuff, at least in part, by arresting or even reversing immunosenescence.
One key approach to keeping our immune age down relates to the fact that as we get older, some of our immune cells start to misbehave.
This is especially problematic for a class of immune cells called neutrophils, the most common type of white blood cell. These form part of the innate immune system, the body’s first line of defence against infection, and are the border force of the immune system, patrolling tirelessly through the bloodstream on the lookout for harmful bacteria.
When they detect an intruder, they squeeze out of the blood vessel and barrel towards their target, then take it out in one of three ways: engulfing it like Pac-Man, spraying it with deadly chemicals or suicidally disgorging their DNA and throwing it around the invader like a net.
The process by which they tunnel through tissues is called chemotaxis, and it becomes increasingly erratic as we age.
Older neutrophils can still detect invaders, but become much worse at hunting them down, often blundering haphazardly through tissue or charging off in the wrong direction. This is problematic for two reasons. It reduces the speed and efficiency of the defence, giving invaders more time to gain a foothold. It also causes inflammation.
These blundering neutrophils also cause between two and five times as much damage as their comrades that still know their way. Such friendly fire is a leading cause of low-level inflammation that creeps throughout our bodies as we age.
But the neutrophil satnav can be reset.
The root of the problem is a chronically overactive enzyme involved in directional control.
Scientists tracked down some existing drugs that were known to dial down this enzyme. When given to older adults, they found that it reset their satnav.
“Their neutrophils are rejuvenated, they move like a young person’s neutrophils,” they stated.
What are these miracle drugs? Statins, the ordinary cholesterol-lowering drugs already taken by millions of people.
Turning to real patient data from the University of Birmingham’s Queen Elizabeth hospital, Lord found that people admitted to hospital with pneumonia were much less likely to die if they were already taking statins to lower their cholesterol.
This staggering result has since been confirmed in a small clinical trial.
We do not recommend that everybody take statins as an immune booster as the drugs can also have serious side effects. But now might be a good time to have your cholesterol levels tested, once your local health system has capacity.
There is also a drug-free way to rejuvenate your neutrophils: exercise.
Measuring exercise levels and neutrophil migration in older adults show that those doing 10,000 steps on average had neutrophils as good as young adults!
It’s important to point out that neutrophils aren’t antiviral so won’t prevent you catching coronavirus or help you beat it, but they will protect you from the real danger, which is pneumonia.
Another class of immune cells that begin to misfire as we age are T-cells.
These are pivotal in the adaptive immune response – the more targeted part of the system – but are blunted in two ways by immunosenescence.
As with neutrophils, their internal signalling pathways go awry but there may be a simple way to undo this damage.
According to Dayong Wu, a nutritional immunologist at Tufts University in Boston, the answer is vitamin E.
In animal studies, it has long been known to enhance immune function, but the relevance of this research to humans was overshadowed by studies suggesting that vitamin E supplementation is toxic.
Wu now says this is irrelevant: toxicity only arises at doses double that needed for T-cell rejuvenation.
He and his colleagues tested vitamin E in older people – giving half of the 670 residents of a nursing home a small daily dose of vitamin E and the other half a placebo – and found significant differences in the rate of upper respiratory infections.
A bigger clinical trial is in the pipeline, but the evidence is already strong enough that Wu recommends people over 65 routinely take 200 international units (IUs) of vitamin E. “It may help immune function. It doesn’t hurt,” he says.
Vitamin D, meanwhile, appears to do the same for the innate arm of the immune system, especially among people living at latitudes where there isn’t enough winter sunlight for their skin to synthesise the molecule.
A 2017 review of the evidence for taking vitamin D supplementation concluded that it prevents upper respiratory tract infections.
About 1000 to 2000 IUs should be safe and beneficial, says Wu, but people shouldn’t go higher than that because big doses actually suppress T-cell function.
A third supplement with good evidence for immune-boosting powers is zinc. “It is very effective for viral infections,” says Wu. Though he adds, “be cautious, the effective window is narrow and an overdose will suppress your immune system”.
Aside from misbehaving immune cells, another big clue about the demise of our immune system with age comes from a vital but little-known organ called the thymus that is (or was) located beneath your breastbone.
This heart-shaped patch of lymphatic tissue is where new T-cells mature before being released on active duty.
It is very active in childhood but degenerates with age, shrinking by about 3 per cent a year from the onset of puberty.
By late middle age, it has usually been reduced to a few scraps, and T-cell counts fall off a cliff. This has consequences for the ability to fend off novel pathogens.
In older people, who barely have any thymus left, the adaptive immune system is severely diminished, leaving an entire flank of their immune defences horribly exposed.
Stepping up thymic regeneration is an active area of anti-ageing research.
A study of 125 amateur cyclists aged between 55 and 79 found that they were leaner, fitter and stronger than average, but they also had better immune systems.
Their T-cell counts were similar to those of much younger people and their thymuses were youthful.
A large part of thymic decline is down to physical inactivity.
There are strong suggestions from animal experiments that exercise might not just prevent thymic degeneration, but also reverse it, although that hasn’t yet been demonstrated in humans.
Exercise has other immune-boosting effects too. “Active skeletal muscle is anti- inflammatory and stimulates macrophages,” says Lord, who goes running every day. “Skeletal muscle is a profound immunoregulatory tissue in the body and keeping it going by physical activity really will have a lot of benefits for health. Exercise benefits all ages.”
Increasing your step count to 10,000 per day will help to strengthen your immune system.
What you eat will also matter to your immune system – now is the time to look after your gut flora.
There is good evidence that probiotics can enhance the immune system, and that poor gut health is a cause of premature ageing and even that a healthy microbiome can reduce your immune age.
There is plenty you can do to maintain a robust gut flora, including eating healthy, varied diet rich in fibre, plant matter and fermented foods such as kimchi.
Other dietary changes, such as fasting, are backed by good evidence too.
None of these interventions is without sacrifice. But if you want to stay alive and well for as long as possible, looking after your immune system is a no-brainer!
The age of your immune system is a critical component of your lifespan.