Background and Aim: Skin tone contributes critically to facial attractiveness; skin aging yellowness has become a predominant aging and skin tone concern in the Asian population. However, the clinical parameters underlying the visual perception of skin yellowness remain elusive. This study explored the relevant clinical parameters and exposome factors influencing the perception of skin yellowness. Methods: Perceived facial skin yellowness was evaluated through three observation and rating tests involving 170 female participants. Standardized lighting and screen settings ensured consistent evaluations of randomized full face and skin‐tone‐adjusted images. The correlation of yellowness observation and clinical parameters was identified, helping to decode the parameters that determine perception. Results: The pair test showed that not only b * but also L * and skin diffused reflection determined yellowness perception commonly across age. Rating test on artificial face images confirmed the importance of both b * and L *. A preliminary model on colorimetric parameters was derived: Perceived Yellowness = 0.42 b * − 0.2 L * + 9.01. Further pair test demonstrated that perceived skin yellowness varied seasonally, suggesting an influence of sun exposure. Conclusion: This study reveals the correlation of skin yellowness perception and clinical parameters, especially the contribution of relevant colorimetric parameters. From a third‐person perspective, b *, L * and diffused reflection are key determinants of perceived skin yellowness. The observed seasonal variation in yellowness perception indicated a perceivable “seasonal skin yellowing.” The findings provided new insights for developing treatments for skin aging yellowness, photoprotection and modulation of colorimetric parameters ( L * and b *) and optical parameter (reflection) are highlighted as important clinical targets.

Psychological stress and poor sleep quality are prevalent among urban adults and have been proposed to be associated with skin, scalp, and hair health through neuro-endocrine-immune pathways. However, evidence from large real-world cohorts under chronic, naturalistic conditions remains limited. The objective of this study was to characterize the associations of sleep quality and perceived stress with a range of dermatological outcomes under real-life conditions, including self-perceived concerns, expert-scored clinical signs, and objective instrumental measurement in healthy women. This cross-sectional observational study enrolled 1,017 healthy women aged 18–40 years in Shanghai, China. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and perceived stress with the Perceived Stress Scale (PSS-10). Dermatological outcomes were assessed through four modalities: validated psychometric questionnaires, self-perception surveys, expert clinical scoring, and objective instrumental measurements. Associations were investigated using generalized linear models (GLMs) adjusted for age and season (regression analytical sample: n=994 after exclusion of participants with BMI>30), with Benjamini–Hochberg correction for multiple comparisons. Poor sleep quality (PSQI score ≥ 6) was identified in 60% of participants and elevated perceived stress (PSS-10 score ≥ 14) in 50%. Both factors were significantly associated with lower wellbeing, happiness, and higher fatigue scores. Poor sleep quality was associated with increased likelihood of reporting sensitive scalp (OR = 1.17 [95% CI:1.08–1.27], Adj-P = 0.004), skin fatigue appearance (OR = 1.11 [95% CI:1.06–1.17], Adj-P = 0.003), and self-perceived skin yellowness (OR = 1.10 [95% CI:1.04–1.15], Adj-P = 0.013), as well as a modest but significant increase in clinically graded dark eye circle severity (β = 0.028 [95% CI: 0.012–0.044], Adj-P = 0.014). Elevated perceived stress was associated with self-reported hair loss (OR = 1.04 [95% CI:1.01–1.06], Adj-P = 0.034) and itchy scalp (OR = 1.07 [95% CI:1.03–1.11], Adj-P = 0.035). In post-hoc exploratory age-stratified analyses, poor sleep was associated with higher acne severity exclusively in participants aged 18–25 years (p = 0.016). In this cross-sectional study of healthy urban women in Shanghai, poor sleep quality and elevated perceived stress were each associated with a range of self-perceived dermatological concerns and clinical signs. These findings are cross-sectional in nature and require longitudinal investigation to establish temporal directionality. The observed associations are consistent with the skin-brain axis hypothesis and support the relevance of sleep and stress assessment in dermatological research and practice.

Skin yellowness is a predominant age-related concern, particularly among North Asian populations, and is suspected to be associated protein carbonylation. However, the precise chemical mechanisms linking skin yellowness and protein carbonylation remain unclear. This study elucidates these mechanisms by investigating the protein yellowing process induced by carbonylation. Employing both in vitro skin models and a protein solution, this study demonstrates that 4-hydroxynonenal (4-HNE), a representative reactive aldehyde generated by lipid peroxidation, triggers protein carbonylation, which subsequently leads to the formation of cross-linked oligomers that visually manifest as yellowness. Characterization via GB1 model protein and its mutants, NMR and MALDI-TOF mass spectrometry reveals that cross-linked oligomers, rather than the initial carbonylation events, are the primary source of protein discoloration. Furthermore, yellow intensity correlates with the size and/or structure of the oligomers. Finally, nucleophilic scavengers such as glutathione (GSH), cysteine (Cys), and histidine (His) are shown to significantly suppress both protein yellowing and oligomerization. These results establish the first mechanistic connection between protein carbonylation and visible discoloration, offering novel insights for targeted dermatological interventions and advancing the understanding of aging biology and protein chemistry.

Extracellular vesicles (EVs) are lipid-enveloped nanovesicles rich in microRNAs, proteins and lipids, that serve as potent mediators of intercellular communication. While EVs have demonstrated pro-regenerative potential in 2D and preclinical models, their impact on skin regeneration and aging processes in 3D reconstructed skin models has remained less explored. In this study, EVs from adipose-derived stem cells and umbilical cord-derived mesenchymal stem cells (UC-MSCs) were evaluated using both 2D primary skin cells and 3D full-thickness reconstructed skin models. EVs stimulated fibroblast and keratinocyte proliferation, increased epidermal thickness, and enhanced the presence of collagen IV in the dermal-epidermal junction (DEJ) and fibrillin 1 in the extracellular matrix. Bulk transcriptomic analysis of the 3D reconstructed skin revealed gene expression profiles impacted by the addition of EVs. Additionally, miRNA-seq and proteomics of extracellular vesicle contents revealed miRNAs and proteins that may be drivers of the biological activities observed in 3D models, suggesting EVs activate processes associated with skin regeneration. This holistic approach demonstrated that EVs previously linked to pro-regenerative behaviors also modulate biomarkers associated with cutaneous aging in full-thickness 3D reconstructed models. This work not only provides mechanistic insights but also paves the way for the development of next-generation regenerative skincare active ingredients.