Background: Skin ageing takes on many different forms. Despite this diversity in skin ageing phenotypes, literature published to date is limited in scope, as many research studies either focus on one single phenotype or just a few specific phenotypes. Presently, phenotypes such as wrinkles, pigment spots, and photo-ageing are receiving most of the research attention. We therefore wonder whether the current discourse on skin ageing places a disproportionate amount of focus on a few selected phenotypes, leaving other skin ageing phenotypes underexplored. Methods: In this cross-sectional study, we performed a broad assessment of forty-one signs of skin ageing and characterised the phenotypes that constituted key components of skin ageing. We also explored the interrelationship among forty-one skin ageing phenotypes using Spearman’s Correlation and Principal Component Analysis. Results: We analysed our study population, which is composed of 3281 ethnic Chinese participants from the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES). The first ten principal components cumulatively explain 46.88% of the variance of skin ageing phenotypes in our study population. We discovered that the commonly discussed forms of skin ageing (i.e., wrinkles, pigmentation, and photo-ageing) only accounted for a small portion (24.39%) of the variance of all skin ageing phenotypes in our study population. Telangiectasia, a poor lip fullness, a lighter skin colour, xerosis, ephelides (freckles), ptosis of eyelids (droopy eyelids), eyebags, and a low eyebrow positioning were other key components of skin ageing, accounting for a further 22.49% of the variance of skin ageing phenotypes in our study population. We found that each of these ten skin ageing phenotypes characterises a key and important aspect of skin ageing. In this broad assessment of skin ageing, we first described the prevalence of forty-one signs of skin ageing and then characterised in detail both the prevalence and severity distribution of ten key skin ageing phenotypes. Conclusions: We presented clear evidence that skin ageing is much more than just wrinkles, pigmentation and photo-ageing. The addition of telangiectasia, poor lip fullness, a lighter skin colour, xerosis, ephelides, ptosis of eyelids, eyebags, and a low eyebrow positioning added more dimensions to skin ageing phenotype presentations. © The Author(s) 2025.

Background: Atopic dermatitis (AD) is a chronic inflammatory itchy skin condition. Genome-and epigenome-wide association studies provide insights into genetic susceptibility and the pathogenesis of potential underlying disease. Objective: This study sought to functionally characterize an AD-associated single-nucleotide polymorphism (SNP) located deep intronic of the tight junction protein 2 (TJP2) gene (9q21.11 locus), identified through a genome-wide association study (GWAS). Methods: The association between the 9q21.11 locus (rs7872806) and AD was identified through a GWAS of 956 cases and 723 controls. TJP2 expression in peripheral blood mononuclear cells (PBMCs) was assessed against the rs7872806 genotype. Allele-specific methylation was evaluated at CpG sites 10 kb up-and down-stream of the 9q21.11 locus. The effect of DNA methylation on TJP2 expression was validated via in vitro methylation and 5-aza-2’-deoxycytidine–induced transcriptional activation studies. Transepidermal water loss (TEWL) measurements were used to determine skin barrier function. Results: The major allele "G" of rs7872806 was found to increase the risk of AD by 2.64-fold (adjusted P value, 2.40 × 10-18; OR, 0.38) and was associated with increased methylation levels at the cg13920460 site (P<.001) and lower TJP2 expression in PBMCs (Pearson P=1.09 × 10-6, Pearson R, –0.313, P<.001). Inhibition of methylation by 5-aza-2’-deoxycytidine increased TJP2 promoter activity by up to 85%. Elimination of the cg13920460 methylation site increased expression by approximately 25%. The major allele of rs7872806 was also found to be associated with increased TEWL (P<.001). Conclusion: Epigenetic influence at CpG site cg13920460 is associated with rs7872806 located deep intronic at 9q21.11. The SNP confers susceptibility to AD by altering TJP2 expression and promoting TEWL. © 2025 Esmon Publicidad.