1. ^*Department of Cytobiology and Cytopathology, Philipps University Marburg, Marburg, Germany
2. ^†R&D, Beiersdorf AG, Hamburg, Germany
3. ^‡Institute of Cell Biology, Swiss Federal Institute of Technology (ETH Zürich), Hönggerberg HPM, Zürich, Switzerland

Correspondence: Dr Thomas Blatt, R&D Cosmed, Beiersdorf AG, Unnastrasse 48, D-20245 Hamburg, Germany. Email: thomas.blatt@beiersdorf.com

Received 2 March 2004; Revised 29 July 2004; Accepted 2 August 2004; Published online 19 January 2005.

Abstract

Cutaneous aging is characterized by a decline in cellular energy metabolism, which is mainly caused by detrimental changes in mitochondrial function. The processes involved seem to be predominantly mediated by free radicals known to be generated by exogenous noxes, e.g., solar ultraviolet (UV) radiation. Basically, skin cells try to compensate any loss of mitochondrial energetic capacity by extra-mitochondrial pathways such as glycolysis or the creatine kinase (CK) system. Recent studies reported the presence of cytosolic and mitochondrial isoenzymes of CK, as well as a creatine transporter in human skin. In this study, we analyzed the cutaneous CK system, focusing on those cellular stressors known to play an important role in the process of skin aging. According to our results, a stress-induced decline in mitochondrial energy supply in human epidermal cells correlated with a decrease in mitochondrial CK activity. In addition, we investigated the effects of creatine supplementation on human epidermal cells as a potential mechanism to reinforce the endogenous energy supply in skin. Exogenous creatine was taken up by keratinocytes and increased CK activity, mitochondrial function and protected against free oxygen radical stress. Finally, our new data clearly indicate that human skin cells that are energetically recharged with the naturally occurring energy precursor, creatine, are markedly protected against a variety of cellular stress conditions, like oxidative and UV damage in vitro and in vivo. This may have further implications in modulating processes, which are involved in premature skin aging and skin damage.