Proteomics of Human Skin Aging: Molecular and Translational Limits

Human skin aging comprises changes in extracellular matrix, epidermal differentiation and barrier function, redox balance, protein homeostasis, inflammation, and senescence. This critical narrative review uses structured descriptive charting of published human skin proteomic evidence relevant to adult aging. Original source identification used non-exhaustive PubMed searches and citation checking through 25 August 2026; revision-time verification searches are documented separately. The source-audited adult corpus comprised 35 reports in 31 report families across direct human skin, explants, and primary cells, with adjacent and contextual sources outside these counts. Findings were grouped post hoc by broad biological domain while retaining specimen, exposure, comparator, analytical endpoint, and validation status. Recurrence concerned broad processes rather than identical proteins, directions, or harmonized pathway statistics. Protein-level comparison was constrained by small cohorts, heterogeneous sampling and inference rules, variable statistical reporting, and scarce external validation. Most bottom-up studies resolved protein groups rather than intact proteoforms; peptide-location and cleavage-susceptibility studies showed why abundance, processing, modification, and structural accessibility are distinct. Direct topical-intervention findings were sparse and formulation-specific. The reviewed literature has not yet established a universal skin-aging signature independently validated across compartments, exposures, and platforms. It supports contextual interpretation and candidate prioritization, while proteomic response alone does not establish biological-age reversal or clinical efficacy.