How to optimise your ageing immune system

Humans are living longer than ever. Longevity is one of the greatest achievements of our modern era. A significant social transformation propelled by improvements in healthcare, sanitation, vaccination and more. But there’s an irony in living longer — we’re more likely to see our bodies and minds decline. Your immune system itself is not immune to age related decline.

As a start example, an average 65-year-old woman in the European Union is expected to live for about another 21.4 years, but only 10.2 of these years are expected to be spent in healthy conditions absent of severe or moderate health problems, while the forecast for men is merely 9.8 years out of the remaining (average) 18.1 years. Perhaps you'll agree that living longer is pretty worthless if we are not also living better in those twilight years?

While ageing itself is not a disease, age-related diseases are illnesses and conditions that occur more frequently as we get older meaning age is a significant risk factor. There are a variety of factors that influence our risk of age-related ill health. The immune system being one of the most significant factors.

Your Immune Age

Your immune-age is what age your immune system “acts” like it is – not your chronological age. The rate of immunological ageing can actually vary considerably between people. Differences are already apparent between people in their 20s. So even if you are still fairly young, mitigating your immunological ageing is something you need to be considering. Immune ageing is of course partly attributed to genetics, but much of it is a consequence of the cumulative effects of our lifestyle, life-load and all the exposures we have experienced.

 

Characteristics of immune ageing

Before we delve into what we can do to improve our immune age, let’s first get to know our immune system a little better since there is a lot more to it than meets the eye.

The immune system comprises so many different components. It includes physical barriers like skin, and the lining of our gut as well as the healthy microbiota that live on and in us. It can be divided into the innate immune system which is a diverse collection of white blood cells and molecules that form our first line of defence. As well as the adaptive immune system made of our T cells and antibody producing B cells. It also encompasses organs including our bone marrow, thymus (The thymus is a specialized primary lymphoid organ of the immune system, located in the upper chest) and lymph nodes.

Our immune system is distributed all over the body. In a sense, this means every single cell, tissue and organ in our entire body encompasses our immune system, making it more like our ‘wellness system’. Consequently, ageing of our immune system can disproportionately drive whole-body ageing.

So what happens when our immune system ages?

Immune cells accumulate damage and can become ‘senescent’. Senescence is a process by which a cell ages and permanently stops dividing but does not die. Senescent immune cells lose their ability to behave in an orderly fashion. Senescent immune cells will, over time, reduce the ‘space’ available for fresh new well-functioning immune cells. This further contributes to the vicious cycle of raised levels of unwanted inflammation known as inflamm-ageing and oxidative stress ³. Oxidative stress occurs when there is an imbalance between free radicals and antioxidants. This results in biological damage to our DNA and the proteins that make up our bodies. Inflammation perpetuates more oxidative stress, which can drive ageing and worsen symptoms.This can accelerate ageing and lead to or worsen a vast number of age-related health conditions over time.

The good news is that studies are now showing that we can roll back the relative age of the immune system!

Change now, for a better later

So, I’ve hinted that there are ways we can improve our immune age, but we also need to steer clear of saboteurs to stay younger and healthier for longer. It’s no secret but smoking is not helpful for your health span so you should definitely try to kick the habit if you can.
Less obvious are things like:

• alcohol
• UV rays from the sun
• exposures to environmental toxins and chemicals
• eating a calorie excessive diet
• being sedentary
• carrying a heavy mental load
• not getting enough sleep.

Epigenetics of ageing

If we think of our DNA as the computer hardware, then epigenetics is the malleable software. Epigenetics flips the ratio of nature vs. nurture on its head. Epigenetics describes changes to the way that genes function without altering the genetic sequence that we were born with. Methylation is one epigenetic mechanism through which we can tag genes to be switched on or off in response to our lifestyle. DNA methylation patterns reflect how your genes react to life. Why am I telling you this? Your immune system is the primary translator of information from how you are living. By epigenetically altering gene pathways involved in the immune system, our daily choices majorly impact our current and long-term health . A recent pilot study demonstrated that just 8-weeks of diet and lifestyle modifications reduced ageing. One of the key interventions in this study was the inclusion of lots of leafy greens and cruciferous veggies combined with moderate exercise, decent sleep, strong social interactions and relaxation practices. Another study showed that individuals following an anti-inflammatory Mediterranean diet for over a year slowed down ageing.

Immuno-metabolism

Healthy metabolic function has to be a part of the discussions around ageing. Metabolism refers to the set of chemical processes that collectively convert food into energy and then use that energy. Metabolism is occurring continuously inside your body to keep you alive and your organs functioning normally, such as breathing, repairing cells, digesting food and of course sustaining the energy needs of our immune system. The mitochondria is the core of all metabolic processes. They are small organelles found in all our cells. It’s where we turn calories into ATP – the energy currency. Metabolism and the immune system are deeply interconnected with the mitochondria, a central hub of the balance and regulation of immunity. Immune responses are energetically demanding processes, requiring large amounts of energy and metabolic building blocks to fuel them. When our immune cells are not engaged in a particular activity, they are relatively metabolically ‘quiet’. Here, mitochondria fulfil the energy demands needed for maintenance. Mitochondria are the metabolic switches needed to transform immune cells quickly into a metabolically active state to carry out specific functions like fighting infection when needed.

Nicotinamide adenine dinucleotide (NAD) is a molecule that is integral to the creation of ATP. Our bodies are able to make NAD but, as we age, our levels start to decline. Recent studies demonstrate that reducing NAD levels is a key causal factor for increasing age-related metabolic decline ⁷. We cannot consume NAD directly from our diet, but we can consume foods that are a source of nutrients like vitamin B3 that help support our bodies to make it. Nicotinamide Riboside (NR) is a form of vitamin B3 that is available as a supplement, which has been clinically tested to support NAD levels.

An apple a day keeps the senescence away

Immune cells have one of three fates as we age:

1. to survive and continue to work effectively
2. to become inflammatory senescent cells
3. or to commit suicide (known as ‘apoptosis’) and make ‘space’ for fresh new immune cells.

Senescent cells might sound sinister, but this transformation is a protective function that occurs when cellular damage is beyond repair. It turns the cell into a protective senescent state in which the cell stops dividing, preventing development of cancers. However, even a relatively low abundance of senescent cells is sufficient to cause dysfunction to our cells and tissues. Senescent cells are rare in young individuals but increase with age. Our ability to remove senescent cells also decreases with age. Increasing senescent cells causes further decreases to our NAD levels and adds to our inflammatory burden, accelerating ageing.

Supporting your body to remove these senescent cells is a promising approach to preventing age-related damage and supporting longevity. Senolytics are substances that help complete the disrupted life-and-death cycle in senescent cells, allowing them to die and reducing the inflammatory burden they cause. This encourages production of new cells and supports the health of surviving cells which has an overall rejuvenating effect on the age of our immune system.

Most senolytics which are being tested are drugs but some lifestyle practices as well as compounds found in the plants that we eat have been identified as having senolytic activity as well as helping to support mitochondrial function, improve oxidative stress and inflammation or exerting beneficial epigenetic effects.

Examples of plant compounds which may have a senolytic effect include:

• Quercetin enriched in onions, apples, grapes and green tea
• Luteolin enriched in celery, parsley, onions, and apple skins
• Fisetin enriched in strawberries, apples and persimmon
• Piperlongumine found in the Long pepper plant
• Curcumin a component of the spice turmeric
• Spermidine found in mushrooms, soy products and legumes/li>
• Resveratrol found enriched in the skin of grapes and other berries.

While it's currently unclear from the research whether regularly eating these foods or consuming supplements containing these plant compounds will have any meaningful effects on your personal senescent burden, we do know that these compounds are plentiful in an anti-inflammatory diet plan like the Mediterranean diet. And eating a diversity of fresh produce is vitally important to reduce unwanted inflammation and oxidative stress which are associated with senescence so definitely worth trying to eat as many fruit and veggies as possible.

Lifestyle practices can also prime our bodies into becoming senescent killing machines. For example, regular exercise has senolytic effects⁷. Fasting and calorie restriction are also promising strategies to kill senescent cells. Fasting and calorie restriction can promote a process known as autophagy which prompts our body to remove damaged cells. Although there is a scientific basis behind these modalities, we still don’t know exactly how long humans would need to fast or calorie restriction to experience these beneficial effects. Therefore, they need to be practiced with caution. Fasting too long or not taking in enough nutrients can actually suppress the immune system and can be accompanied by a host of other negative effects ⁸. There is now a diet, developed by anti-ageing researchers at the University of Southern California, that mimics the effects of fasting for those too frail to skip meals.

Final word

There is no doubt that we can slow down our ageing clock and science is now revealing the answer as to how. With such a complex issue as ageing, there is never going to be a one-size-fits- all approach, but you are never too old (nor too young) to start including some anti-ageing strategies discussed in this article into your daily routine. Supporting your health, particularly in your latter years, means that you can still get so much enjoyment from life and continue to do all the things that you love.

Dr. Jenna Macciochi is an immunologist specialising in understanding how nutrition and lifestyle interact with the immune system in health and disease.

Currently With over 20 years' experience she is on a mission to break down the science behind our health and share the secrets of how to be well, for good. Based in Brighton, Jenna is a lecturer at Sussex University, a qualified fitness instructor and health coach and author of Immunity: the science of staying well.

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