One of the most visible changes associated with the aging process in humans relates to a progressive thinning of the skin. This results from a decline in both collagen and glycosaminoglycans, as well as from changes in their chemical structure and 3-dimentional organization. Transdermal administration of antioxidants, a -lipoic acid (LA) (0.5%) and proanthocyanidin PA) (0.3%) in a standard cosmetic vehicle base formulation supplemented with 2% benzyl alcohol as a penetration enhancer, a mixture of essential amino acids (0.2%), significantly enhanced collagen synthesis and deposition. The amino acid mixture was designed to mimic serum concentrations, with supplemental methionine added to provide additional sulfur. The histological appearance of the skin of mature female rats treated in this fashion reflected the increased deposition of collagen in the dermis as well as a thickened epidermal layer. The changes do not seem to be mediated by TGF- ss or PDGF, two growth factors known to stimulate collagen synthesis. At lower concentrations, a -lipoic acid did not affect cell proliferation but at higher doses, while it had an inhibitory effect on (3)H-thimidine uptake, it did enhance collagen production. Pronanthocyanidin did not affect cell proliferation but significantly increased collagen synthesis by cultured fibroblasts.