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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.

Intrinsic (chronological) skin ageing is characterized by atrophy of the skin with loss of elasticity and slowed metabolic activity. The superposition of environmental damage, particularly exposure to ultraviolet radiation (photodamage), on the intrinsic ageing process results, at least initially, in a hypertrophic repair response, with a thickened epidermis and increased melanogenesis. Even more striking changes occur in the dermis: massive elastosis (deposition of abnormal elastic fibres), collagen degeneration, and twisted, dilated microvasculature. Regular use of a sunscreen alone appears to allow some repair as well as protection from further photodamage. Topical tretinoin has been shown to partially reverse the clinical and histological changes induced by the combination of sunlight exposure and chronological ageing. A formulation of tretinoin in an emollient cream (Retinova, Renova), developed specifically for the treatment of photodamaged skin, has been extensively investigated in multicentre, double-blind trials and has been shown to produce significant improvement within 4-6 months of daily use, compared with vehicle alone, as part of a regimen including sun protection and moisturizer use. Histological changes in the epidermis and dermis noted after 12 months suggest tretinoin repairs photodamage by reconstitution of the rete pegs, repair of keratinocyte ultrastructural damage, more even distribution of melanocytes and melanin pigment, deposition of new papillary dermal collagen, and improvements in vasculature. Alpha-hydroxy acids (AHAs) have also been widely used for therapy of photodamaged skin, and these compounds have been reported to normalize hyperkeratinization and increase viable epidermal thickness and dermal glycosaminoglycans content. The single randomized controlled study now available appears to substantiate AHA efficacy and safety. In summary, recent work has substantially elucidated the ageing processes that affect the skin and has demonstrated that many of the unwanted changes can be improved by topical therapy.

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