While I was researching the impact of TNF-alpha on skin aging and related cytokines, I came across this paper which looked interesting… out of UCSF (but done with a Korean skin cream company). I’m thinking that this might be a good “base” into which I could add my senolytic drug mixture.
As humans get older, we experience a low-level of inflammation—dubbed “inflamm-aging”—driven by an increase in molecules in the blood called cytokines. This age-related inflammation has been linked to serious chronic diseases, including Alzheimer’s disease, cardiovascular disease, and diabetes. Scientists initially thought that the inflammation stemmed from the immune system or the liver, but a group of dermatologists at UCSF have a different theory.
“The inflammation must come from an organ big enough that very minor inflammation can affect the whole body. Skin is a good candidate for this because of its size,” said study senior author Mao-Qiang Man, MD, a research scientist in the UCSF Department of Dermatology, who is based at the San Francisco VA Health Care System and is also a visiting professor at Southern Medical University in Guangzhou, China. “Once we get old, we have dermatological symptoms like itchiness, dryness, and changes in acidity. It could be that the skin has very minor inflammation, and because it’s such a large organ it elevates circulating cytokine levels.”
Our skin starts to deteriorate around age 50 with changes to epidermal pH, hydration, and the permeability barrier, which keeps water in and bacteria and other potential pathogens out. A loss of moisture and breaks in the permeability barrier cause the skin to release inflammatory cytokines. Ordinarily, these cytokines help to repair defects in the barrier, but in aging skin the barrier can’t be fixed as easily, so the inflammatory signals continue to be released, eventually reaching the blood.
“Until recently, the scientific community didn’t believe that skin could contribute to systemic inflammation and disease. But in the last five years, studies of psoriasis and dermatitis have shown that skin inflammation from these diseases likely increases the risk of heart disease," said study lead author Theodora Mauro, MD, a professor of dermatology at UCSF and the San Francisco VA Health Care System. “Aging skin is much more common than psoriasis or dermatitis, so the overall risk to the population from aging skin could far outweigh that seen from skin diseases. Decreasing inflammation simply by treating the skin dysfunction seen in aging could have profound health effects.”
In the study, published March 5, 2019 in the Journal of the European Academy of Dermatology and Venereology, Mauro, Man and colleagues attempted to reverse age-related skin damage using an over-the-counter skin cream formulated based on prior research by Man and colleagues, and which the researchers had previously shown to contribute to skin repair based on its beneficial ratio of three types of lipids (cholesterol, free fatty acids, and ceramides) that are vital for skin health.
Thirty-three older adults between the ages of 58 and 95 applied the cream all over their bodies twice a day for 30 days. After a month, the researchers measured blood levels of three cytokines—interleukin-1 beta, interleukin-6, and tumor necrosis factor (TNF) alpha—that have all been implicated in age-related inflammatory diseases. Using the cream reduced the amount of all three cytokines compared to both the participants’ levels before using the cream and the levels of similarly aged adults who did not use the cream. In fact, using the cream lowered participants’ cytokine levels to be nearly equivalent with people in their 30s, suggesting that rejuvenating the skin can reverse “inflamm-aging.” The cream also improved skin hydration, lowered pH, and repaired the permeability barrier.
Related research paper:
Topical applications of an emollient reduce circulating pro-inflammatory cytokine levels in chronically aged humans: a pilot clinical study
Because a previous study had shown that topical applications of Atopalm® (Supplemental Table 1), an over-the-counter, triple lipid formulation (Neopharm, South Korea), improves epidermal function in humans8, we chose this formulation. The entire skin surface of the treated, aged subjects was treated topically with ≈3ml of this formulation twice-daily for one month, while the parallel, aged cohort remained untreated. To ensure consistency in the volume of cream applied, as well as the timing of each application, all topical applications were performed by designated, trained staff. The untreated, young control group were recruited from the residents of Dalian City. This pilot study was carried out during the early Spring (i.e., from March 14 to April 14, 2017), to prove the concept that improvements in epidermal function can lower circulating levels of cytokines.
Paper: (pay walled): https://onlinelibrary.wiley.com/doi/10.1111/jdv.15540
Full Paper from Sci-Hub: Sci-Hub | Topical Applications of an Emollient Reduce Circulating Pro-Inflammatory Cytokine Levels in Chronically Aged Humans: A Pilot Clinical Study | 10.1111/jdv.15540
I think this is the product used in the study:
Amazon Atalopalm “store”: Amazon.com: ATOPALM
Ingredients of the product used in the study (not sure how it matches up with above cream):