Age-related redistribution of zinc and copper within human skin

BACKGROUND: The skin's natural functions rely on essential metals such as zinc and copper, which contribute to cell growth, differentiation, and apoptosis. With ageing, low-grade inflammation (inflammaging) develops, and zinc deficiency in skin becomes more common. Data on the distribution of these metals in human skin are limited and there is no information on how the distribution changes with age. OBJECTIVES: Establishing the spatial distribution of zinc and copper in human skin is a first step towards addressing their functions in specific cell layers and skin structures. METHODS: Laser ablation inductively coupled plasma mass spectrometry was employed to map zinc (⁶⁶Zn) and copper (⁶³Cu) in human female Caucasian abdominal and facial skin from young, middle-aged, and older donors at 5-8 µm spatial resolution. A novel bespoke integration method with gelatine micro-droplet standards enabled semi-quantitative comparisons. RESULTS: In facial skin, zinc concentrations are approximately three- to five-fold higher in the epidermis than in the dermis, whereas qualitative data from abdominal skin show a similar epidermis-enriched zinc signal and were used primarily for method development. In facial skin, copper levels remain relatively uniform between these layers. Facial skin samples from older donors demonstrate increased zinc accumulation in deeper layers, elevated copper levels, and altered copper-to-zinc ratios. Within skin structures, a significant age-related copper enrichment in hair follicles and eccrine sweat glands is observed. CONCLUSIONS: The innovative approach not only pushes the technical limits of mass spectrometric metal imaging but also uncovers novel insights into age-dependent metal redistribution in human skin. Our investigation opens exciting avenues for developing metal-based biomarkers to improve skin health and combat skin ageing.