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Photoageing is the superposition of chronic ultraviolet (UV)-induced damage on intrinsic ageing and accounts for most age-associated changes in skin appearance. It is triggered by receptor-initiated signalling, mitochondrial damage, protein oxidation and telomere-based DNA damage responses. Photodamaged skin displays variable epidermal thickness, dermal elastosis, decreased/fragmented collagen, increased matrix-degrading metalloproteinases, inflammatory infiltrates and vessel ectasia. The development of cosmetically pleasing sunscreens that protect against both UVA and UVB irradiation as well as products such as tretinoin that antagonize the UV signalling pathways leading to photoageing are major steps forward in preventing and reversing photoageing. Improved understanding of the skin's innate UV protective mechanisms has also given rise to several novel treatment concepts that promise to revolutionize this field within the coming decade. Such advances should not only allow for the improved appearance of skin in middle age and beyond, but also greatly reduce the accompanying burden of skin cancer.

The major differentiated function of melanocytes is the synthesis of melanin, a pigmented heteropolymer that is synthesized in specialized cellular organelles termed melanosomes. Mature melanosomes are transferred to neighboring keratinocytes and are arranged in a supranuclear cap, protecting the DNA against incident ultraviolet light (UV) irradiation. The synthesis and distribution of melanin in the epidermis involves several steps: transcription of melanogenic proteins, melanosome biogenesis, sorting of melanogenic proteins into the melanosomes, transport of melanosomes to the tips of melanocyte dendrites and finally transfer into keratinocytes. These events are tightly regulated by a variety of paracrine and autocrine factors in response to endogenous and exogenous stimuli, principally UV irradiation.

Alzheimer's disease is a neurodegenerative disorder characterized by the extracellular deposition in the brain of aggregated ␤ -amyloid peptide, presumed to play a pathogenic role, and by preferential loss of neurons that express the 75-kD neurotrophin receptor (p75 NTR ). Using rat cortical neurons and NIH-3T3 cell line engineered to stably express p75 NTR , we find that the ␤ -amyloid peptide specifically binds the p75 NTR . Furthermore, 3T3 cells expressing p75 NTR , but not wild-type control cells lacking the receptor, undergo apoptosis in the presence of aggregated ␤ -amyloid. Normal neural crest-derived melanocytes that express physiologic levels of p75 NTR undergo apoptosis in the presence of aggregated ␤ -amyloid, but not in the presence of control peptide synthesized in reverse. These data imply that neuronal death in Alzheimer's disease is mediated, at least in part, by the interaction of ␤ -amyloid with p75 NTR , and suggest new targets for therapeutic intervention. ( J. Clin. Invest. 1997.

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