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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.

Abstract

Background

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.

Objective

We performed a pilot study to determine whether improving epidermal function reduces circulating proinflammatory cytokine levels in aged humans.

Methods

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.

Results

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.

Conclusion

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.

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About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.
  1. March 18, 2019

    One of the authors of this study is also on the executive team for the cream studied…seems to be a conflict of interest.

    • mm
      March 18, 2019

      Yes, it is possible so really larger scale replication is required. Also, it is not unusual for such conflicts of interest in research. Researchers are of course developing therapies with the hope to commercialize them and naturally make money in doing so, so these things happen and at least the conflict is openly declared. Fortunately, this is not a difficult study to replicate and confirm via blood draw. I am always mindful when such conflicts exist but it does not always mean we should dismiss them immediately either. Independent replication will go a long way towards that end.

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