Deposition of mature collagen is increased by topical ROL in aged human skin in vivo. OCT-embedded skin sections (7μm) were obtained from aged (76±6 years) healthy sun-protected buttock skin after topical treatment of vehicle and 0.4% retinol for seven days. (A) Nanoscale collagen fibrils were imaged by AFM. Representative AFM images were shown. N=12. The blue arrows indicate intact collagen fibrils and red arrows heads indicate damaged collagen fibrils. (B) Three dimensional collagen fibrils. Dermal roughness was analyzed using Nanoscope Analysis software (Nanoscope_Analysis_v120R1sr3, Bruker-AXS, Santa Barbara, CA). All results are expressed as the mean ± SEM, N=12, *p < 0.05. Bars=100 nm. (C) Proposed model for topical ROL exerts anti-aging effects in aged human skin by proliferation of epidermal keratinocytes and dermal endothelial cells and activation of dermal fibroblasts (see Discussion for details).