The Skin May Hold the Answers to What Ails the Body

Researchers are trying to find out if moisturizing your skin could have systemic health benefits

ToTo prevent chronic disease, eat well, sleep seven to nine hours a night, exercise… and perhaps you should also moisturize your skin. Yes, moisturize. According to ongoing research at the University of California, San Francisco, certain moisturizers could be unexpected allies in the prevention of chronic disease after middle age.

To understand the mechanism of this potential protective effect, we have to look at the relatively recent concept of “inflammaging” (a combination of inflammation and aging). As people get older, they experience an increase in the levels of certain molecules, called pro-inflammatory cytokines, which amplify inflammation in the body. This is thought to be one of the reasons behind a chronic inflammatory process in the elderly, which was first referred to as “inflammaging” in a 2000 article by immunology professor Claudio Franceschi and his team at the University of Bologna in Italy. (When that process starts may vary from person to person depending on genetic traits. But several studies that measured inflammation in people over 60 have found an ever-increasing inflammatory status.)

In a perfect world, inflammation is part of the body’s immune response and plays an important role in fighting invaders such as viruses and bacteria and repairing damaged tissue. But some researchers believe persistent low-level inflammation in the elderly seems to be the common denominator of many age-related conditions such as Alzheimer’s, cardiovascular disease, Type 2 diabetes, and degenerative arthritis.

But what does all of this have to do with moisturizers? “What we have found, much to everyone’s surprise, was that those inflammatory cytokines are coming from the skin,” says UCSF dermatology professor Dr. Peter Elias.

Research led by Elias found that in the process of aging, the skin barrier — which normally protects the body from excessive water loss — becomes more permeable and slowly loses its ability to keep the skin hydrated. As a response to this barrier defect and the resulting dehydration, the skin sends out signals (inflammatory cytokines) to try to repair that flaw. The problem is that, in aged skin, all those signals get sent out day after day without ever actually being able to repair the defect because of intrinsic problems of the aged skin. Those cytokines eventually end up circulating in your blood, possibly causing a state of low-grade, whole-body inflammation.

EElias’ team first observed this issue in mice. Much like elderly humans, aged mice also have a defective skin barrier that prevents it from holding moisture in. The researchers measured the levels of cytokines both in the skin and in the blood of aged mice. In comparison with eight-week-old mice (considered young adults in mice age), 12-month-old mice (considered middle-aged) had increased levels of several types of inflammatory cytokines, in addition to drier skin. To prove that the increased inflammatory signals in the blood were actually coming from the skin, not from other organs, the scientists also measured the cytokine levels in the liver, which were not increased.

The elevation of skin-related cytokines happens naturally and gradually starting from the age of 50 and is present even in people without any apparent dermatological symptoms. In those with actual inflammatory skin conditions such as psoriasis, characterized by scales and red patches, the increased inflammatory cytokine levels have already been found to be associated with a higher risk of cardiovascular disease, according to work by dermatology professor Joel Gelfand and his team at the University of Pennsylvania. (Researchers are now investigating whether the use of drugs that block one of such cytokines may bring that cardiovascular risk down in psoriasis patients.)

If an inflammatory skin condition such as psoriasis seems to be increasing the risk of chronic disease through the elevated levels of inflammatory signals, then the same process could be happening in naturally aged skin, hypothesized UCSF dermatology professor Dr. Theodora Mauro. “The question that we asked was: Can we decrease the systemic inflammation seen in aging by decreasing whatever inflammatory signals the skin might be sending out?”

As the skin is the largest organ in the human body, treating even part of it might have a big enough impact.

Mauro’s and Elias’ team then decided to investigate if a topical treatment to improve the skin barrier could help treat age-associated systemic inflammation. They’ve shown that, by applying a moisturizing agent twice daily over the aged mice’s whole body, not only does skin inflammation go down, but the overall blood levels of inflammatory cytokines also drop. As moisturizing agents, they’ve tested either 200 milligrams of petroleum jelly (Vaseline), or 60 microliters of glycerol.

The same effect was observed in humans. In a small clinical trial, participants ages 58 to 95 applied a moisturizing cream all over their body twice a day. At the end of 30 days, the overall levels of three inflammatory cytokines that have been associated with aging — interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNFα) — went down.

This suggested an exciting possibility, says Mauro. “That the increased inflammation in aged people, which was thought of as normal, isn’t in fact normal, but it’s instead tied to a decrease in skin function. If you improve the skin function, you can improve the inflammation seen in aging.”

And because the circulating cytokines that begin to accumulate with aging are thought to be responsible for downstream disorders like Type 2 diabetes, Alzheimer’s, and chronic arthritic conditions, the impact of moisturizing could go beyond the skin. “If we can restore the skin barrier and decrease the generation of those cytokines that get into the blood, then perhaps we can prevent downstream development of those chronic disorders” says Elias, adding that new experiments are in progress to test the actual impact of moisturizing in the prevention of chronic disease in the long term.

While the role of chronic mild inflammation in the process of aging has been intensely investigated over the past two decades, the potential role of the skin in this process is still in its early stages of research, which means that larger studies are still needed to confirm whether treating aging skin can really have a systemic health benefit.

BBut would any moisturizer be able to decrease chronic inflammation? In the clinical study mentioned earlier, the cream used by volunteers contained three types of lipids: ceramides, cholesterol, and fatty acids. Previous work by the UCSF team had shown that this combination can successfully repair the skin barrier in the long term because it mimics the proportion of the lipids naturally present on the skin. Together, they form a type of mortar that fills the spaces between the skin cells. According to the UCSF study, moisturizers that don’t contain those lipids, or contain them in the wrong proportion, may cause an imbalance that leads to the formation of holes in this mortar. The result is that the product will only briefly soothe the skin, which will feel even drier moments later.

At the moment, though, there are not a lot of options of creams with the triple-lipid composition, and the available ones, including prescription-only Epiceram and over-the-counter Atopalm, available online, are more expensive than most drugstore moisturizers.

The good news is that the researchers have been testing several other moisturizing options.

“In terms of inflammation, the cheaper moisturizers seem to work just as well, regardless of whether they are able to restore the skin barrier in the long term or whether they are just working as an artificial barrier,” says Mauro.

What the researchers also want to find out in their forthcoming studies is exactly how much of the skin you would need to moisturize in order to bring down the inflammatory signals. “I’m hoping that you get substantial lowering if you apply moisturizers just once a day to the legs, for example,” says Elias. As the skin is the largest organ in the human body, treating even part of it might have a big enough impact.

Science and health journalist with a special interest in evidence-based medicine and epidemics. Columbia Journalism School alumna. mari.lenharo@gmail.com.

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