Mass spectrometry‐based proteomics reveals the distinct nature of the skin proteomes of photoaged compared to intrinsically aged skin

Abstract

Objective With increasing age, skin is subject to alterations in its organization, which impact on its function as well as having clinical consequences. Proteomics is a useful tool for non‐targeted, semi‐quantitative simultaneous investigation of high numbers of proteins. In the current study, we utilize proteomics to characterize and contrast age‐associated differences in photoexposed and photoprotected skin, with a focus on the epidermis, dermal–epidermal junction and papillary dermis. Methods Skin biopsies from buttock (photoprotected) and forearm (photoexposed) of healthy volunteers (aged 18–30 or ≥65 years) were transversely sectioned from the stratum corneum to a depth of 250 μm. Following SDS‐PAGE, each sample lane was segmented prior to analysis by liquid chromatography‐mass spectrometry/mass spectrometry. Pathway analysis was carried out using Ingenuity IPA. Results Comparison of skin proteomes at buttock and forearm sites revealed differences in relative protein abundance. Ageing in skin on the photoexposed forearm resulted in 80% of the altered proteins being increased with age, in contrast to the photoprotected buttock where 74% of altered proteins with age were reduced. Functionally, age‐altered proteins in the photoexposed forearm were associated with conferring structure, energy and metabolism. In the photoprotected buttock, proteins associated with gene expression, free‐radical scavenging, protein synthesis and protein degradation were most frequently altered. Conclusion This study highlights the necessity of not considering photoageing as an accelerated intrinsic ageing, but as a distinct physiological process.

An overview of extracellular matrix and its remodeling in the development of cancer and metastasis with a glance at therapeutic approaches

“…It was demonstrated that the level of collagen is reduced at a rate of 1% annually in different tissue types 9 . Additional to intrinsic factors, extrinsic factors such as the skin photo‐aging phenomenon can also accelerate the aging process by modulating the matrix proteomic combination 69 . In recent years, it has been shown that aging matrix has a tight correlation with cancer 70 .…”

Peptide location fingerprinting reveals modification‐associated biomarker candidates of ageing in human tissue proteomes

“…Protein entities pertinent to these pathways were subsequently used to build pathway-or protein class-specific, experimentally identified interaction networks. MatrixDB (Launay et al, 2015) was used to derive ECM proteins interactions and IntAct (Orchard et al, 2014) for all others. These were then downloaded and visualised using Cytoscape 3.4.0.…”

“…Label-free proteomic liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful analytical technique used traditionally for the identification and relative quantification of proteins within complex tissue extracts. The technique has enabled the identification of disease and ageing biomarkers based on their relative abundance (Newton et al, 2019); however, the detection of abundance-independent, modification-associated biomarkers in complex protein mixtures remains challenging.…”

Towards Precision Dermatology: Emerging Role of Proteomic Analysis of the Skin

“…As mentioned, its complexity results in difficulties in separating and homogenizing the tissue for mass spectrometric analyses, and the dominance of structural proteins further complicates the process. Consequently, until recently, prior studies have only identified a relatively small fraction of the expressed skin proteome [21,22,33,[35][36][37][38][39]. For example, Mikesh et al [33] analyzed the composition in three skin layers from two anatomical regions, resulting in characterization of about 200 proteins and providing insight into varying protein composition depending on skin layer and skin region.…”