Molecular mechanisms of skin aging: state of the art.

The process of skin aging in humans is complex and is induced by multiple factors, including genetic and various environmental ones. In particular, the superposition of environmental factors, such as UV irradiation on skin, results in massive wound-like morphological alterations mainly of the dermis. In sun-protected areas the most pronounced changes occur within the epidermis and affect mostly the basal cell layer. As a result, while sun-protected aged skin appears thin, finely wrinkled, and dry, photoaged skin is characterized by deep wrinkles, laxity, and roughness. Although the fundamental mechanisms are still poorly understood, a growing body of evidence points toward the involvement of multiple pathways in the generation of aged skin. Recent data obtained by expression-profiling studies and studies of progeroid syndromes (e.g., Hutchinson-Gilford progeria, Werner syndrome, Rothmund-Thomson syndrome, Cockayne syndrome, ataxia teleangiectasia, and Down syndrome) illustrate that among the most important biological processes involved in skin aging are alterations in DNA repair and stability, mitochondrial function, cell cycle and apoptosis, ubiquitin-induced proteolysis, and cellular metabolism. One of the major factors that has been proposed to play an exquisite role in the initiation of aging is the physiological hormone decline occurring with age. However, hormones at age-specific levels may not only regulate age-associated mechanisms but also regulate tumor-suppressor pathways that influence carcinogenesis. Understanding the molecular mechanisms of aging may open new strategies in dealing with the various diseases accompanying aging, including cancer.