P33 Molecular profiling identifies innate immune drivers of skin ageing in Asian populations
Rhea Pai, Jing Hui Low, Anand Kumar AndiappanAbstract
Introduction and aims
Skin ageing is increasingly recognized as a systemic process driven by chronic, low-grade inflammation resulting from age-associated immune dysregulation. Sustained activation of innate immune pathways contributes to epidermal barrier dysfunction, delayed wound repair, and increased susceptibility to inflammatory skin disorders. However, insights into inflammageing are predominantly derived from White cohorts, limiting their relevance to Asian populations. Accordingly, this study aims to characterize systemic and innate immune signatures associated with skin ageing in Asian populations to reveal clinically actionable biomarkers of inflammageing.
Methods
We recruited 110 healthy volunteers aged 21–90 years across Singapore’s three major ethnic groups: Chinese, Malay and Indian. Skin tissue biopsies and peripheral blood samples were collected, together with standardized questionnaires and skin physiological measurements. To characterize innate immune tissue interactions, peripheral blood was analysed using high-dimensional flow cytometric profiling, alongside plasma-based inflammatory profiling using the Alamar NULISA® Inflammation Panel. Integration of cellular immunophenotyping with secretomic analyses enabled quantification of age- and ethnicity-associated shifts in innate immune cell subsets.
Results
Flow cytometry revealed age-associated alterations in two key innate immune subsets. Older individuals exhibited significantly reduced basophil activation, characterized by diminished CD63 degranulation and reduced CD203c expression following house dust mite stimulation. Monocyte populations were also skewed towards a nonclassical phenotype with ageing. These changes suggest impaired innate immune functionality with potential consequences for skin-resident immunity, antimicrobial defense, and type 2 immune responses. Consistent with these findings, plasma nucleic acid-linked immuno-sandwich assay profiling identified elevated cytokines associated with innate immune dysregulation in older participants. Collectively, our results underscore the importance of evaluating immune ageing beyond conventional adaptive immune compartments, such as T cells, and highlight monocytes and basophils as key innate immune contributors of ageing.
Conclusions
In conclusion, molecular profiling uncovered innate immune mechanisms driving skin ageing and identified clinically relevant biomarkers in Asian populations, with implications for personalized treatment and care strategies.