Seamus C. C. Phan
This study synthesizes current knowledge on bioactive peptides for adult and aging skin, integrating skin structure, aging biology, peptide classes, formulation science, preclinical models and clinical evaluation to inform evidence-based topical strategies. Skin architecture and ageing mechanisms are summarized to contextualize peptide interventions that target epidermal renewal, dermal extracellular matrix, pigmentation and inflammation. Peptide categories covered include signal peptides that promote collagen, elastin and glycosaminoglycan synthesis, carrier peptides that deliver trace metals such as copper, neurotransmitter-modulating peptides for expression lines, and enzyme-inhibiting sequences that reduce MMP and tyrosinase activity. Case examples describe Pal-KTTKS, Pal-GHK, Cu-GHK, tripeptide-10 citrulline, SA1-III (KP1) and Pep 14, highlighting modes of action from collagen fibrillogenesis control and MMP activity reduction to modulation of PP2A/AKT and senescence-associated signaling. Formulation considerations examine physicochemical constraints on cutaneous delivery, lipidation strategies, nanocarriers, cell-penetrating peptides, stability challenges and vehicle design that balance penetration with safety. Mechanistic assays spanning fibroblast and keratinocyte monolayers, 3D skin equivalents and ex vivo human skin are presented alongside clinical and instrumental endpoints including profilometry, ultrasound, histology and DNA methylation age metrics. Safety, sensitization, regulatory labeling and claim frameworks are discussed with recommendations for rigorous trial design, standardized measurements and population-specific risk assessment for aging skin. Practical guidance addresses regimen sequencing, combination with retinoids and procedures such as laser, microneedling and fillers, emphasizing controlled evaluation to optimize matrix remodeling, repair and tolerability in mature skin.