Chronic inflammatory skin diseases such as pediatric atopic dermatitis and hidradenitis suppurativa (HS) are linked with accelerated epigenetic aging among patients, new data suggest, although results vary by disease and additional standardized research is needed.1
A review highlighting epigenetic clocks or biomarkers that allow for different insights into the systemic impacts of chronic inflammatory diseases such as HS and atopic dermatitis. The data included in this review resulted from an analysis by investigators such as Ajay S. Dulai, MBBS, from Integrative Skin Science and Research in Sacramento, California.
Dulai and coauthors highlighted that epigenetic clocks can be classified into those that are intrinsic and those that are extrinsic. Intrinsic clocks, they noted, rely only on methylation changes, whereas extrinsic clocks involve immune cell composition as part of their algorithm.2
“The application of epigenetic clocks provides valuable insights into the systemic effects of chronic inflammatory diseases,” Dulai and colleagues wrote.1 “These clocks may serve as potential biomarkers of both inflammation and the factors that may control inflammation in the future. This review aims to summarize published studies that have identified variations in epigenetic aging in individuals with chronic dermatological conditions.”
Review Details and Findings
The investigators’ review looked specifically at human studies evaluating patients’ epigenetic ages in relation to dermatological conditions such as HS and atopic dermatitis. They only deemed English-language manuscripts as eligible, excluding non-English publications from their search of available databases. These databases included Embase, PubMed, and Web of Science
All of Dulai et al’s search results were imported into Rayyan to streamline their selection of literature. Titles and abstracts were initially screened independently by a set of reviewers. Data deemed relevant according to criteria for eligibility were advanced to a full-text review and, when disagreements took place in this process, they were settled by reevaluating the full-text manuscripts to attain a consensus.
Later, data extraction was conducted and the findings assessed by Dulai and colleagues were organized. Information collected from each study included the type of dermatological condition under investigation, principal findings, the epigenetic clock employed, sources of tissue samples, and number of study participants. There were 2 commonly implemented measures of epigenetic aging: AgeDiff and Aging Ratio.
AgeDiff represents the absolute gap, assessed in years, between an individual’s epigenetic age and their chronological age. A positive AgeDiff would suggest an accelerated biological aging process, meaning the body appears older than their true chronological age. Conversely, a negative AgeDiff would indicate slowed or decelerated aging, where the biological profile is younger than the person’s chronological age.
The Aging Ratio expresses this relationship as a percentage, illustrating the relative pace of aging throughout one’s lifetime. A positive ratio would point to faster-than-expected aging, whereas a negative value points to slower biological aging. Given the heterogeneity the investigative team noted among these studies, a meta-analysis could not be conducted. The authors noted, however, that such an analysis may become feasible once more standardized research and consistent methodologies are available.
Ultimately, there were 6 studies that the investigative team found met the inclusion criteria. These comprised 4 investigating psoriasis, 1 assessing atopic dermatitis, and 1 focusing on HS. Based on the Oxford Levels of Evidence, 4 of these studies were determined to be level 4 evidence, 1 as level 5, and 1 as level 3. The findings varied by condition. In those with psoriasis, individuals with concomitant psoriatic arthritis, but not psoriasis alone, were noted by the team to have significantly accelerated epigenetic aging compared with controls. In atopic dermatitis, pediatric patients displayed evidence of increased biological aging, measured across several clock models, including the Horvath, Skin and Blood, PhenoAge, and GrimAge clocks. Among those with HS, subjects exhibited elevated biological age when tissue samples were collected from impacted skin regions.
Collectively, these results suggest a potential link between chronic inflammatory skin diseases and accelerated biological aging, although the pattern differs by condition and disease context.
The review emphasized the need for further studies to clarify the relationship between disease severity and measures of epigenetic aging. Expanding investigations into a broader range of skin disorders could help identify shared pathways between inflammation, aging, and dermatological health. Additionally, there is a need for refinement of epigenetic clocks to capture inflammatory signatures more accurately and to integrate skin-specific biomarkers. Such tools would improve the precision of biological age estimation in chronic skin conditions and potentially provide insights into long-term disease burden.
“Future work is needed to correlate epigenetic aging with dermatological disease severity and treatment outcomes,” they concluded.1 “Additionally, this review highlights the need for developing skin-specific methylation clocks, which can be trained on validated markers of skin aging and biophysical functionality.”
References
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AS Dulai, A Joshi, M Min, et al. Systematic Review of Accelerated Epigenetic Aging in Chronic Inflammatory Dermatology Conditions. International Journal of Dermatology (2025): 1–8,
https://doi.org/10.1111/ijd.70055 . -
Beynon RA, Ingle SM, Richmond RC, et al. Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer. Clin Epigenetics. 2022 Jan 3;14(1):1. doi: 10.1186/s13148-021-01220-4. PMID: 34980250; PMCID: PMC8725548.