IN WINTER, the backs of your hands may become dry, red and cracked. Maybe you find yourself slathering on moisturiser. If you donāt, the itching and pain can become a major distraction.
You might think that is as far as it goes: cracked skin is annoying and uncomfortable, but not serious in the same way as, say, high blood pressure. But that assumption, like ageing skin, might not hold water.
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Growing evidence suggests that damage to the skin can have knock-on effects for the rest of the body, driving inflammation, muscle and bone loss, and possibly even cognitive decline. The more your skin deteriorates, the more the rest of you ages prematurely. In this emerging view, your skin doesnāt just reflect signs of ageing ā itās a contributing factor. There is even tentative evidence that taking better care of our skin could slow the harmful effects of ageing and improve our overall health.
Our skin is one of the first parts of the body to show signs of ageing. It becomes wrinkly, especially in active places like the corners of our eyes, and age spots can appear. Such changes may seem ā quite literally ā skin-deep, but we shouldnāt underestimate the skinās importance to the rest of the body. āThe skin is the largest organ in the body,ā says at Augusta University in Georgia, US.
And it isnāt just about size. The skin is crucial for survival. The outer layer, the epidermis, is impermeable to water, ensuring that we donāt lose our life-giving fluids to the air. If someone damages large swathes of the top layer of their skin, or their skin otherwise stops functioning as an effective barrier, they are at severe risk of death, says at the University of California, San Francisco. This is one of the reasons why blistering diseases and severe burns are so dangerous. āPeople have understood that since biblical times,ā she says.
Nevertheless, the medical establishment has only recently realised that even less extreme skin damage can have serious effects. āPeople are just now coming around to the idea that inflammatory skin disease can affect your body as a whole,ā says Mauro.
Much of the evidence for this link comes from two skin conditions: and (also known as atopic eczema). In psoriasis, the skin produces too many new cells, forming patches of flaky, scaly skin. In atopic dermatitis, some areas of the skin are dry, cracked and itchy. Both tend to be chronic conditions requiring lifelong management.
Decades of evidence indicate that these conditions are linked with a higher risk of severe harms. A of 19 studies concluded that atopic dermatitis was associated with a āsmall but significantā increase in the risk of heart attack, stroke, angina and heart failure. Similarly, have concluded that people with psoriasis seem to be at disease than those without it. Skin conditions are also . āThe association is pretty strong,ā says Mauro.
Of course, correlation isnāt causation: just because these skin conditions are associated with a range of other health outcomes doesnāt necessarily mean they are causing them. However, evidence is building that there really are causal links. Both psoriasis and atopic dermatitis lead to , says , also at the University of California, San Francisco. In response, skin cells try to repair the barrier. To do so, they release chemical signals called cytokines that trigger inflammation.
āThe purpose of inflammation is to activate the immune system and to promote healing of wounds,ā says Bollag. An inflamed tissue is red, swollen and painful. More blood flows to it and its temperature rises. These are all signs that the bodyās healing systems are getting to work. āThe issue is that sometimes it doesnāt resolve when it should,ā says Bollag. Inflammation is meant to be a short-term response, but if it persists, it can become harmful. That is exactly what happens in chronic skin conditions like psoriasis.
Inflammation
Inflammation also plays a role in ageing. For , researchers have explored a phenomenon called āā in which older people display chronic, low-level inflammation. Their blood constantly has slightly compared with younger people. This continual, low-grade inflammation has been linked to a , including dementia, arthritis and type 2 diabetes. It may also , the same sort of muscle loss that was shown to be associated with skin conditions.
āThe intellectual leap that my group made was to say, well, these inflammatory cytokines youāre seeing in the blood as people age are the exact same inflammatory cytokines that you see when you insult the skin,ā says Mauro.
To demonstrate this, she teamed up with Elias and other researchers, including at the Southern Medical University in Guangzhou, China. In 2017, they disrupted the skin of mice by placing cellophane tape on it and then stripping it off. Three hours later, the genes that code for cytokines were being expressed more in the miceās skin and cytokine levels in their blood rose. However, when the team restored the skinās barrier by applying glycerol or petroleum jelly, again.
The key may be disruption to the very outermost layer of the epidermis, known as the stratum corneum, or āhorny layerā. This is made up of dead skin cells enriched in a protein called keratin, and it is crucial to keeping water inside the body. In 2023, researchers led by Man looked at the skin and blood of 255 people aged 65 or older. The researchers found that people with .
Emerging evidence also suggests inflamed skin can contribute to inflammatory bowel disease. For example, a led by at the University of California, San Diego, investigated why skin inflammation and inflammatory bowel disease often go together. It found that when the skin of mice became inflamed due to injury or infection, a chemical called hyaluronan was released. This entered the gut and triggered an immune response.
Skin damage may also , according to a 2022 study by Wenquan Liang, also at Southern Medical University, and his colleagues. Mice whose skin had been damaged in a way that mimicked ageing lost bone mass. The team linked this to skin cells releasing less of a protein called cystatin-A, which normally regulates the behaviour of bone cells. When the damaged skin produced less of it, the bone cells behaved abnormally and the bones became weaker. Smearing a chemical called calcipotriol on the miceās skin triggered the production of cystatin-A and .
The effects of skin damage may even reach into the brain, says Elias. āThereās an association now that we have shown, convincingly, for Alzheimerās and dementia,ā he says. A number of studies have found that people with inflammatory skin diseases are . Indeed, other research has also suggested that plays a role in the development of .
Barrier defects
Another important factor in the skinās impact on our well-being is via touch (see āThe importance of touchā, below), but perhaps the most obvious ā albeit overlooked ā way this organ shapes our health is that a weaker skin barrier, caused either by disease or by ageing, could allow harmful chemicals and particles to sneak into the body and cause more widespread damage. āWhat my lab has been working on, and what weāre getting close to showing, is that there is an additional barrier defect in ageing, which is that things get in there,ā says Mauro. She points to a 2021 study that tracked appointments at dermatology clinics following the 2018 California wildfires. People who had been exposed to the air pollution from the fires were more likely to report that .
Despite the growing evidence for the impact of our skin on our overall health, plenty of uncertainty remains. For one thing, it isnāt clear to what extent these changes are being driven by the skin ā as opposed to the skin being caught up in something that is being driven by another organ.
āWe donāt really know yet whether the things we measure in skin are a reflection of systemic health influencing the skin or whether, because of the size of the organ, changes in, for example, immune cells that are resident in skin are influencing systemic health,ā says , executive director of A*STAR Skin Research Labs in Singapore. āThereās still some debate as to whatās driving the process.ā
Mauro says that there is a lot of cross-talk between different bodily systems, so it probably isnāt an either-or situation. And even within the skin, multiple mechanisms seem to be at work. One factor is zombie-like senescent cells, which build up as we age, not just in the skin but throughout the body. āThey donāt die, but theyāre not normal, and it turns out theyāre pretty inflammatory,ā says Mauro.
Microbiome
for the importance of the skin microbiome in all this. Like other parts of our body, the skin is home to a huge variety of microorganisms, including bacteria, fungi and viruses. āUntil recently, it was not appreciated how much the microbiome affects the skin and then how much the skin affects systemic health,ā says Gallo. We now know that a healthy skin microbiome helps , as well as enhancing the barrier function of skin and regulating the activity of skin cells.
For instance, Galloās team has spent years investigating a species of bacterium called Staphylococcus aureus, which lives on our skin and can become infectious. Healthy skin is good at fighting this microbe off, but people with atopic dermatitis often have greater numbers of S. aureus on their skin than those without. āPart of it is the bodyās immune problems leading to increased susceptibility to [bacterial] growth,ā says Gallo. His team has found that , which could then have implications for the rest of the body.
Other bacteria on the skin matter too. Some other Staphylococcus species, such as Staphylococcus hominis, . But people with atopic dermatitis have fewer of these helpful bacteria. āPeople with that disease have parts of their healthy microbiome that are missing,ā says Gallo. This means S. aureus can run wild, making the atopic dermatitis worse and driving up inflammation.
Skin treatments
The obvious implication of all this is that treatments that improve our skin could also improve our overall health, reducing our risk of a range of conditions, not least cardiovascular disease or dementia. There is already evidence of this for people with skin conditions. āIf you treat psoriasis, there are less heart attacks,ā says Gallo.
In theory, this could apply to everyone: as our skin ages and starts driving inflammaging, skin treatments could reduce the effect. However, few supposedly anti-ageing skin treatments have been rigorously tested in high-quality randomised controlled trials. A rare exception is research conducted by Watson in 2009 and her colleagues, which showed that one over-the-counter skincare product (the manufacturer of which funded the study) could improve signs of skin ageing, . āThat was a great big surprise,ā she says. āWe went into the research with healthy scepticism.ā
But could the effects of skin creams go beyond the skin? In 2019, Man, Mauro, Elias and their colleagues tried to find out. In a , they gave 33 older people a skin cream containing three types of skin lipids ā cholesterol, free fatty acids and ceramides ā twice a day for 30 days. (Man and Elias were consultants to the productās manufacturer at the time of the research.) Compared with controls, those who used the cream had skin that became better at retaining water, and levels of cytokines in their blood fell.
Building on this, in 2022, Elias, Man and their colleagues went back to the purported link between damaged skin, inflammation and brain function, and decided to see if repairing older peopleās skin could alleviate cognitive deterioration. They recruited 200 people aged over 65 from two Chinese cities. Half were given the skin cream to be applied twice a day between the colder months of November and May each year for three years. The other half got nothing. Over the three years, the control group showed increasing water loss through the skin and steady cognitive decline. The people given the cream had a more hydrated stratum corneum, and .
Mauro emphasises that these studies are only pilots. So while the results are āpromisingā, she says, āI donāt think the evidence is strong enough yet that we can say thereās an absolute benefit.ā Watson points out a further uncertainty: ethnicity. We know that people with different skin colours have subtly different skin structures and that their skin ages differently, so the most effective treatments may vary between people.
There is also the issue of which serums and creams to use, out of the vast range available. Traditionally, skin moisturising lotions have been based on petroleum products, which coat the skin in a water-repellent lipid layer. More recently, however, ābarrier repairā formulations, containing specific lipids that become depleted in the outer layer of our skin when it dries out, have been developed, and there is some evidence to show that compared with traditional moisturisers.
Some skin experts recommend products containing glycerine, which acts as a humectant, drawing water into the skin. āIf youāre going to put on lotion, make sure itās got lots of glycerine,ā says Bollag. There is decades of evidence that it improves barrier function, she says. Beyond this, lifestyle choices can help. āMuch of this is kind of common sense,ā says Watson. You need some sunlight because it drives the production of vitamin D in your skin, but donāt get too much and avoid sunburn.
Reverse skin ageing
Looking far into the future, we may one day be able to completely rejuvenate our skin: in 2022, researchers created a method that can turn back the biological clock on skin cells by 30 years, by exposing them to molecules that reverse development. But until then, it may be worth paying more attention to soothing that irritated skin.
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The importance of touch
Our skin is a major sensory organ, detecting pain, itching and temperature ā as well as the often-overlooked sensation of touch.
Anyone who lived alone through the covid-19 lockdowns will know the importance of touch. , and if you go too long without being touched, it can take a toll on your mental health. In a 2023 paper, at the Netherlands Institute for Neuroscience in Amsterdam and his colleagues conducted a . Drawing on 212 studies, they found that touch could reduce feelings of depression and anxiety in children and adults.
Mounting evidence shows that touch can benefit our physical health too. For instance, being touched can , a stress hormone. . Likewise, being deprived of touch is bad for you: babies and children who aren't touched .
Packheiser and his team's study found that for most people, it didn't matter whether they were being touched by someone familiar or a healthcare professional. However, newborn babies got the most benefit from being touched by their parents: this even helped them to gain weight faster.
Michael Marshall is a science writer based in Devon, UK, and author of The Genesis Quest
