Inflammaging in Dermatology: A New Frontier for Research

February 2021 | Volume 20 | Issue 2 | Original Article | 144 | Copyright © February 2021


Published online January 25, 2021

Abid Haque MD,a Heather Woolery-Lloyd MDb

aHoward University, College of Medicine,Washington, DC
bUniversity of Miami, Miller School of Medicine, Frost Department of Dermatology and Cutaneous Surgery, Miami, FL

macrophages as illustrated in Figure 1. Zhuang et al published a comprehensive table of mediators of inflammaging in the skin; a modified version of this table can be found in Table 2.

Interestingly, it has been shown that the gastrointestinal tract’s microbiome plays a central role in inflammaging and metaflammation as it’s at the intersection of diet, metabolism, and innate immune response.Thus, the gut microbiome has far reaching effects. It regulates things like the circadian rhythm and sleep patterns through the production of melatonin as well as influences cardiovascular health. In fact, a healthy gut microbiome may even be protective and is associated with healthy aging and longevity.36-39

The effects of the cutaneous microbiome on systemic health has been less researched; although, like the gut, it may have the potential to influence overall health. The cutaneous microbiome is vast, and each square centimeter is home to several million microbes.40 The role of the skin’s microbiome in common dermatologic diseases like atopic dermatitis and psoriasis has been well elucidated. We know that restoring a healthy microbiome in atopic patients reduces the risk of flares and secondary infections41-43 and that in psoriasis a decrease in the diversity of the skin flora increases the risk of flares and arthritis.44,45 These conditions have also been noted to result in increased levels of pro-inflammatory cytokines, which can have serious systemic sequalae such as the increase in cardiovascular risk seen in psoriatic patients.41,46-49

One of the most interesting recent studies regarding the role of inflammaging in dermatology examines how a healthy skin barrier may systemically reduce inflammation.50 Increased levels of inflammatory cytokines in the elderly have been linked to the development of age-related chronic disorders. In mice models, epidermal dysfunction in aged mice has been linked to elevated cytokine levels systemically. Interestingly, in these mice models, improving epidermal function reduced systemic cytokine levels.51 Ye et al studied the effect of daily application of a barrier cream on cytokine levels in older adults.The active group (adults over 65, n=33) applied 3mL of a ceramide- based emollient topically twice-daily for 30 days. The control groups (adults over 65, n=25, adults under 30, n=11) used no topical skincare during the trial. Changes in epidermal function and levels of three key, age-related, plasma cytokines were measured at baseline and after treatment.

The researchers focused on IL-1β, IL-6, and TNF-α because they are considered primary biomarkers of inflammaging.4 As expected, at baseline, the cytokines were elevated in the aged population vs younger cohort. Topical application of the barrier repair emollient significantly enhanced epidermal barrier function and stratum corneum hydration as measured by a multifunctional skin physiology monitor (MPA5; Courage– Khazaka Electronic GmbH). At the end of 30 days, IL-1β and IL-6 normalized, and TNF-α levels declined substantially in the active treatment group. In the control group over 65 and the younger cohort, there was no significant change in IL-1β, IL-6, andTNF-α. This study is interesting because it is one of the first clinical trials to show how skin barrier dysfunction may contribute to systemic inflammaging.

CONCLUSION

Research in aging-related inflammation is an emerging field.5,52 Growing research suggests that reduction in systemic inflammation or inflammaging may directly correlate with a reduction in the risk of developing age-related diseases including