Abstract:  Ultraviolet radiation (UVR) in sunlight has deleterious effects on skin, while behavioural changes have resulted in people gaining more sun exposure. The clinical impact includes a year‐on‐year increase in skin cancer incidence, and topical sunscreens alone provide an inadequate measure to combat overexposure to UVR. Novel methods of photoprotection are being targeted as additional measures, with growing interest in the potential for systemic photoprotection through naturally sourced nutrients. Omega‐3 polyunsaturated fatty acids (n‐3 PUFA) are promising candidates, showing potential to protect the skin from UVR injury through a range of mechanisms. In this review, we discuss the biological actions of n‐3 PUFA in the context of skin protection from acute and chronic UVR overexposure and describe how emerging new technologies such as nutrigenomics and lipidomics assist our understanding of the contribution of such nutrients to skin health.

Elastic fibers comprising fibrillin microfibrils and elastin are present in many tissues, including the skin, lungs, and arteries, where they confer elasticity and resilience. Although fibrillin microfibrils play distinct and tissue-specific functional roles, it is unclear whether their ultrastructure and composition differ between elastin-rich (skin) and elastin-poor (ciliary body and zonule) organs or after in vitro synthesis by cultured cells. Here, we used atomic force microscopy, which revealed that the bead morphology of fibrillin microfibrils isolated from the human eye differs from those isolated from the skin. Using newly developed pre-MS preparation methods and LC-MS/MS, we detected tissue-specific regions of the fibrillin-1 primary structure that were differentially susceptible to proteolytic extraction. Comparing tissue- and culture-derived microfibrils, we found that dermis- and dermal fibroblast–derived fibrillin microfibrils differ in both bead morphology and periodicity and also exhibit regional differences in fibrillin-1 proteolytic susceptibility. In contrast, collagen VI microfibrils from the same dermal or fibroblast samples were invariant in ultrastructure (periodicity) and protease susceptibility. Finally, we observed that skin- and eye-derived microfibril suspensions were enriched in elastic fiber– and basement membrane–associated proteins, respectively. LC-MS/MS also identified proteins (such as calreticulin and protein-disulfide isomerase) that are potentially fundamental to fibrillin microfibril biology, regardless of their tissue source. Fibrillin microfibrils synthesized in cell culture lacked some of these key proteins (MFAP2 and -4 and fibrillin-2). These results showcase the structural diversity of these key extracellular matrix assemblies, which may relate to their distinct roles in the tissues where they reside.

Background Skin health declines with age and this is partially attributed to immunosenescence. Mast cells (MCs) are innate immune cells which coordinate tissue immune responses integral to skin homeostasis and disease. Objectives To understand how MCs contribute to human skin ageing, we investigated how intrinsic ageing impacts MC phenotype and MC relationships with other immune cells and skin structures. Methods In photoprotected skin biopsies from young (≤30yrs) and aged (≥75yrs) individuals immunostaining and spatial morphometry were performed to identify changes in MC phenotype, number, distribution and interaction with the vasculature and nerve fibres. Quantitative PCR was used to measure changes in gene expression related to immune cell activity and neuropeptide signalling. Results Skin MCs, macrophages and CD8⁺ T‐cells increased in number in intrinsically aged, as compared to young skin, by 40%, 44% and 90% respectively (p<0.05), whilst CD4⁺ T‐cells and neutrophils were unchanged. In the aged, MCs were more numerous in the papillary dermis, showed a reduced incidence of degranulation (50% lower than in young; p<0.01), a conserved tryptase/chymase phenotype and co‐expression of granzyme B. In aged skin, MCs increased their association with macrophages (~48% cf ~27%; p<0.05) and nerve fibres (~29% cf 16%; p<0.001), whilst reducing their interactions with blood vessels (~34% cf 45%; p<0.0001). Additionally, we observed modulation of vasoactive intestinal peptide (VIP; increased) and substance P (decreased) gene expression with age; this was associated with an increased frequency of VIP⁺ nerve fibres (~3x higher in aged skin; p<0.05), which were strongly associated with MCs (~19% in aged cf 8% in young; p<0.05). Conclusions Hence, in photoprotected skin, we observe an accumulation of MCs with increasing age; these MCs have both altered functionality and distribution within the skin which supports a role for these cells in altered tissue homeostasis during ageing.