Aging Skin as a Significant Source of Systemic Chronic Inflammation

Researchers here propose that the skin is a significant source of the systemic chronic inflammation that is observed in older individuals. Setting aside the range of other mechanisms that contribute to inflammation to only consider the accumulation of senescent cells with age, and the fact that these errant cells are a potent source of inflammatory signaling, this proposition doesn't seem unreasonable. The skin is a sizable organ, after all, and even if it produces senescent cells at much the same pace as the rest of the body, it will still represent a large and quite distributed pool of such cells, positioned to delivery their inflammatory signals throughout the body.

Increasing evidence points to a provocative role of sustained, sub-clinical inflammation, often termed "inflammaging," in the development of these chronic disorders. In support of this notion, chronologically aged humans (≥50 years) display elevated circulating levels of pro-inflammatory cytokines, particularly IL-6, IL-1β, and TNFα. Moreover, subjects with chronic cutaneous inflammatory diseases, such as psoriasis and eczematous dermatitis, also display an increased prevalence of aging-associated disorders, including atherosclerotic cardiovascular disease, obesity, and type 2 diabetes. Though anti-inflammatory regimens, such as inhibitors of IL-1βα and TNFα, as well as methotrexate, have been deployed in the management of these aging-associated disorders, the outcomes of treatments with these agents have been inconclusive.

While many chronologically aged humans merely display marked evidence of inflammation, they nonetheless display elevated circulating levels of cytokines, suggesting that one or more, as yet identified organs, could account for the aging-associated increase in circulating cytokines. It seems reasonable to postulate that the responsible organs must be large enough to sustain such an increase in circulating cytokines, even without noticeable inflammation. Although the musculoskeletal system is the largest organ in humans, most chronologically aged humans display no evidence of musculoskeletal inflammation.

Other relatively large organs to be considered include the skin, intestines, lungs, and liver. The skin weighs about 20 lbs (with an additional, variable contribution from subcutaneous adipose tissues), while the weights of the intestines, lungs, and liver represent ≈7.5, 5.0 and 3.3 lbs, respectively. Because of their relatively lesser size, inflammation of the lungs, intestines, and liver likely would not only need to be apparent, but also sustained if any of these organs could account for the increase in circulating levels of cytokines. Yet again, the majority of otherwise normal aged humans display few clinical signs or symptoms of inflammation in these organs. Hence, it seems unlikely that they could contribute substantially to "inflammaging" unless multiple organs simultaneously exhibit mild inflammation. Notably, the aged skin commonly exhibits signs and symptoms of inflammation, such as pruritus and senile xerosis.

Because of its relatively large size, we hypothesized that the skin could be an important contributor to the elevated levels of circulating cytokines in chronologically aged humans, despite the fact that it typically displays little evidence of inflammation. Not only its size, but also its unique anatomic site, serving as the interface between the body and external environment, supports our hypothesis. In this site, it is continuously exposed to external physical and chemical stressors, which themselves can provoke inflammation, even as other less-exposed organs remain quiescent. In addition, chronologically aged humans display alterations in several key epidermal functions, each of which can provoke low-grade, chronic inflammation in the skin.



This is an interesting reversal of the usual perspective of skin. It is usually viewed as passive and heavily influenced by the body's biochemistry. And Wow, I did not realize skin weighed that much, I had to do my own calculations to verify it.

Posted by: JohnD at January 23rd, 2020 8:32 AM

This paper is from the same authors that published a paper on using Atopalm skin cream to suppress circulating inflammation. See: 'opical Applications of an Emollient Reduce Circulating Pro-Inflammatory Cytokine Levels in Chronically Aged Humans: A Pilot Clinical Study.'

Posted by: Mark at January 23rd, 2020 10:10 AM

I've been applying Atopalm to the face and Cerave to the rest of my body after every shower. I plan on starting Rapamycin cream this week.

Posted by: Larry at January 23rd, 2020 1:51 PM

Also worth noting is that extremely dilute (0.005%) bleach (sodium hypochlorite) baths may have beneficial effects --
"Bleach could reverse ageing, study finds"
"Study Suggests Bleach Can Reverse The Aging Process"

It would be interesting to know whether other topical Nf-kappab blockers would also work.

Posted by: L Pagnucco at January 23rd, 2020 9:09 PM

@L Pagnucco
For the very least, bleach can make the age spots face 😛 :)

Posted by: Cuberat at January 23rd, 2020 9:27 PM

Autopalm is wonderful, I jumped on it after that study and love how much better my skin feels. cerave is similar with the same studied lipid ratio and a lot cheaper. I still prefer autopalm, South Korea does seem well ahead of us on skin care products.

What specific functions were they referring to?
"chronologically aged humans display alterations in several key epidermal functions, each of which can provoke low-grade, chronic inflammation in the skin."

Posted by: august33 at January 23rd, 2020 9:39 PM

@L Pagnucco

Also worth noting is that bleach (sodium hypochlorite) may have not so beneficial effects.

'Hypochlorite induces Systemic Sclerosis in the mouse'

'Since HOCl is presented here as a potential therapeutic agent in skin diseases, it must be stressed that exposure of skin to HOCl can also be terribly hazardous. Indeed, we have shown in 2009 that daily injections of HOCl into the skin of mice can induce in six weeks almost all the clinical and biological features of systemic sclerosis. ...'

'...the dramatic effects on keratinocytes after only two weeks in the paper by Leung et al., along with the lack of data on dermal impact must prompt clinical investigators to be very cautious if they decide to try such protocol in humans as suggested by the authors.'

Posted by: Jones at January 24th, 2020 5:47 AM

That paper is well worth noting.
Also worth noting is that periodontal rinses with far higher concentrations than 0.005% have been used - so possibly topical vs. injection is the key issue.
I am curious whether topical natural nf-kappaB inhibitors (e.g., mangiferin) may also work.

Posted by: L Pagnucco at January 24th, 2020 2:09 PM

Thanks L Pagnocco for the FYI on bleach baths. I had thought about trying them since they are recommended for eczema, but wondered if they might age the skin - good to know it's the opposite. Most eczema OTC remedies are aimed at improving skin barrier function so should be good for reducing systemic inflammation.

Mangiferin is component of mango leaf tea; it is also an NLRP3 inflammasome inhibitor.

Posted by: CD at January 27th, 2020 1:56 PM

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