NEW YORK — Chronic age-related inflammation is being evaluated as a critical driver of wrinkles, collagen depletion, and other features of progressive skin aging in an area of research that might lead to anti-inflammatory therapies that prevent the complications of aging skin and improve its appearance.

Not least of the factors driving this research are the parallels between the molecular processes shared by aging skin and inflammatory skin diseases, according to Helen He, MD, assistant professor in the Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City.

“The overlap between inflammaging and inflammatory skin diseases raises the question of whether such diseases as atopic dermatitis serve as a therapeutic model for slowing skin senescence,” He said.

Anti-Inflammatories Might Be Relevant to Aging

More specifically, “Can some of the immunomodulatory interventions that have been so successful over the past several years in inflammatory skin diseases be applicable to skin aging,” she said, articulating a question that she is exploring.

The term inflammaging was coined to characterize the close relationship between inflammation and age-related diseases across organs, including the heart, lungs, brain, and liver. Related to immunosenescence, which describes age-related dysregulation of the immune system, this has become an intensive area of research beyond dermatology.

Yet, there is a reason to predict that anti-inflammatory therapies might be particularly useful for modifying aging as it relates to the skin, He reported.

“Inflammatory skin diseases have been undergoing a tremendous translational revolution thanks in large part to skin and blood molecular profiling,” she explained at the 6th Inflammatory Skin Disease Summit.

She and her colleagues at Mount Sinai have contributed to this effort with their ongoing work in developing a multiomic map of healthy and aging skin using biopsies, serum, and tape strips. They are not alone among research centers pursuing inflammation as a targetable driver of aging skin, which is based largely on developing a better understanding of the molecular pathways of skin aging.

Citing evidence that the “skin transcriptome becomes progressively more inflamed with age,” He said that these age-related changes have substantial parallels with the transcriptome of multiple inflammatory skin diseases, including but not limited to atopic dermatitis.

Based on work performed so far, He reported that upregulation of immune cytokines from the T-helper type 2 pathway as well as the type 17 and type 22 pathways are among those that have attracted attention for their participation in an inflammaging skin phenotype. This observation was drawn from work in multiomic mapping.

“We measured more than 350 proteins across multiple inflammatory panels associated with elevated systemic inflammation,” He said. A correlation was found between inflammatory markers in the blood and those in the skin, a relationship potentially relevant to hitting both systemic and cutaneous inflammation targets to slow the aging process as it relates to skin.

Age-Related Molecular Changes Explored in Skin

This work has involved the study of tissues obtained with biopsies and of blood samples, but tape strips are being increasingly employed at He’s center for monitoring inflammatory changes because they are less invasive and easily repeated.

“Biopsy has been the gold standard, but there are many limitations,” He said, pointing to the difficulty of enrolling subjects in sufficient numbers willing to provide biosamples obtained invasively. Repeated biopsies of the face, for example, are impractical even if this is the most important target for preventing age-related changes.

There is now substantial evidence that the non-scarring and largely painless adhesive tape strips placed on skin can capture enough biomarkers to assess pathologic activity, including inflammation, to distinguish abnormal from healthy skin. These might eventually be useful for monitoring response to therapies at the molecular level.

It is reasonable to suspect that optimal results from a therapy that prevents skin aging will require indefinite suppression of inflammation, as do many chronic inflammatory skin diseases. However, inflammaging of the skin might be far more complex, involving both a systemic and a localized effect.

Several systemic therapies, such as metformin and rapamycin, are already being evaluated for inflammatory-related aging processes. These are not necessarily relevant to the skin, but He is hopeful that a more complete multiomics map of skin inflammaging might play a role in evaluating markers of skin inflammation that could be applied to these types of systemic therapies.

People with inflammatory skin diseases, such as atopic dermatitis, show signs of premature aging of the skin, according to He, but inflammation is not necessarily the whole story. The degree to which aging related to exposure to free radicals, sun, and adverse metabolic changes is related to or distinct from inflammaging is uncertain.

Interest in inflammaging is not new. This is a major area of research for Saranya P. Wyles, MD, PhD, dermatologist and researcher at the Mayo Clinic in Rochester, Minnesota, who was asked to comment on this topic. She credited Luigi Ferrucci, MD, PhD, the scientific director of the National Institute of Aging, for defining the role of inflammaging in human aging. His work captures the relationship of upregulation of inflammatory biomarkers with age across physiologic systems, not just the skin.

At Mayo Clinic, Wyles, in partnership with the National Institutes of Health, has been looking at molecular biomarkers and metabolomics of skin tissue collected across age groups within the Baltimore Longitudinal Study of Aging, which was initiated more than 60 years ago.

“We are evaluating how skin could provide clues for chronic diseases with a particular emphasis on inflammation,” Wyles, who has published frequently on this topic, told Medscape Medical News. In regard to the skin in particular, she was the first author of a recent paper, Skinspan, a trademarked effort to revolutionize dermatologic care and extend the healthspan of the skin by finding mechanisms of aging that might be targeted therapeutically.

Again, although it is clear that there are multiple intrinsic and extrinsic factors driving age-related changes in the skin, inflammation is a major focus of research that might lead to clinical tools for slowing the process.

“It is reasonable to believe that the molecular changes in the skin might provide important insight about aging process in general and about how they might be modified in the skin specifically,” Wyles said.

Some of He’s research at Mount Sinai has been supported by a grant from Clinique; she reported having no other disclosures. Wyles reported having no potential conflicts of interest.