The skin is our first line of defense against invading pathogens, and scientists at UC San Francisco and the San Francisco Veterans Administration (VA) Health Care System believe that it may be a cause of inflammaging, the age-related chronic inflammation that encourages a number of age-related diseases to develop.
As we age, we generally experience a rise in this low-grade chronic inflammation, thus increasing our risk for developing a variety of age-related diseases. There are a number of proposed sources of inflammaging, including senescent cell accumulation, cell debris, immunosenescence, and increasing bacterial burden.
In a previous article, we talked about the potential role of bacterial burden in relation to the microbiota of the gut and the age-related failure of the gut membrane, which allows bacterial contamination to invade the body and increase bacterial burden and inflammation. The gut microbiota has been proposed to be an origin point of inflammaging, and researchers suggest that the skin could be another.
The results of a new human pilot study suggest that regular moisturizing of the skin by using cream may also reduce the level of inflammaging. This makes sense, as the skin acts as a barrier to pathogens just as the gut wall membrane does, and a compromise of either allows bacterial products deeper entry into the body and raises the potential for infection and inflammation.
These researchers believe that inflammaging must begin with an organ large enough that even minor inflammation can affect the entire body. They suggest that the largest organ, the skin, is the origin point for inflammaging.
They propose that as we age, there are various dermatological changes that lead to dry and cracked skin, irritation, changes to skin pH, and increased permeability of the skin barrier, which allows bacteria and other pathogens to infiltrate the body. These things then lead to low-grade inflammation, and because the skin is so large, it has the potential to increase the pro-inflammatory cytokines circulating in the bloodstream.
During the study, the researchers attempted to see if they could reverse age-related skin damage using over-the-counter skin creams. The skin cream they used was formulated based on the results of a previous study by members of the same team and included three kinds of lipids, namely cholesterol, free fatty acids, and ceramides. The previous study suggested that these three in the correct ratio support skin repair.
A total of thirty people aged 58-95 used the cream on their bodies twice a day for a total of 30 days as part of the study. Following this, the researchers examined circulating cytokines in the blood of the participants and noticed that levels of interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha were all reduced. These three cytokines, when found in elevated amounts, are indicative of inflammation, and their presence is associated with a number of age-related diseases.
The reduced activity of these key pro-inflammatory cytokines placed the study’s participants in a similar range to 30-year-olds, suggesting that using the cream was able to reverse some aspects of skin aging and address inflammaging somewhat. The researchers demonstrated that the cream was also able to facilitate skin barrier repair, lower pH, and helped hydrate the skin.
The researchers will now follow up with a study that will see if using this cream to reduce inflammaging also delays the onset of age-related diseases associated with inflammation.
While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of aging‐associated chronic disorders (e.g., cardiovascular disease, type II diabetes, osteoporosis and Alzheimer’s disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age‐associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels.
We performed a pilot study to determine whether improving epidermal function reduces circulating proinflammatory cytokine levels in aged humans.
Thirty‐three aged humans were treated twice‐daily for 30 days, with ≈3 ml of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age‐related, plasma cytokines (IL‐1β, IL‐6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system.
We also found significantly higher baseline levels of IL‐1β, IL‐6 and TNFα in aged vs. young humans (p<0.001), as previously reported. Topical applications of the barrier repair emollient significantly enhanced epidermal permeability barrier function (p<0.01) and stratum corneum hydration (p<0.05). In parallel, circulating levels of IL‐1β and IL‐6 normalized, while TNFα levels declined substantially.
The toll that bacterial burden takes on our bodies and its role in aging is only really just starting to become appreciated. The failure of the various barriers that our bodies use to keep pathogens at bay is increasingly becoming noticed as an important part of why we age and a basis for therapies that are focused on keeping those membranes working. Perhaps, something as simple as applying such a formulated cream daily might be a practical measure that any of us could do today to potentially delay aging.
That said, it is worth noting that two of the study authors in this paper also serve as advisors to Neopharm, Ltd the manufacturers of AtoPalm, the cream used in this study. This does not necessarily invalidate the results of the study but it is something to be considered when evaluating the results. It would certainly be good to see a larger scale independent study replicating these results before a final conclusion is made.