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Molecular mechanisms of cutaneous ageing To interpret the effects of dermatological peptides, the molecular alterations of cutaneous ageing must be understood: Intrinsic ageing (chronological) Decreased collagen synthesis by fibroblasts (1% per year after 30) AGE accumulation (Advanced Glycation End-products) by non-enzymatic glycation Fibroblastic senescence with SASP (Senescence-Associated Secretory Phenotype), chronic pro-inflammatory secretion Dermal atrophy , reduced vascularisation, loss of subcutaneous adipocytes Extrinsic ageing (photoageing) UV-B damage : cyclobutane pyrimidine dimers, keratinocyte DNA alteration UV-A and oxidative stress : ROS, lipid peroxidation, protein carbonylation MMP overexpression (MMP-1, MMP-3, MMP-9) via AP-1 activation, degrading collagen and elastin Solar elastosis : accumulation of degraded and dystrophic elastin in the dermis Dermatological peptides act at different levels of these cascades: anabolic stimulation (GHK-Cu, Matrixyl), catabolic inhibition (MMP modulation), anti-oxidant protection (GHK-Cu), inflammatory signalling modulation

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10.1016/j.jsbmb.2016.07.016 147 WeingrtnerO.LtjohannD.JiS.WeisshoffN.ListF.SudhopT.et al (2008)