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.

Until now, the glycation reaction was considered to be a nonspecific reaction between reducing sugars and amino groups of random proteins. We were able to identify the intermediate filament vimentin as the major target for the AGE modification N ⑀ -(carboxymethyl)lysine (CML) in primary human fibroblasts. This glycation of vimentin is neither based on a slow turnover of this protein nor on an extremely high intracellular expression level, but remarkably it is based on structural properties of this protein. Glycation of vimentin was predominantly detected at lysine residues located at the linker regions using nanoLC-ESI-MS/MS. This modification results in a rigorous redistribution of vimentin into a perinuclear aggregate, which is accompanied by the loss of contractile capacity of human skin fibroblasts. CMLinduced rearrangement of vimentin was identified as an aggresome. This is the first evidence that CML-vimentin represents a damaged protein inside the aggresome, linking the glycation reaction directly to aggresome formation. Strikingly, we were able to prove that the accumulation of modified vimentin can be found in skin fibroblasts of elderly donors in vivo, bringing AGE modifications in human tissues such as skin into strong relationship with loss of organ contractile functions.

(2017) A new topical panthenol-containing emollient: Results from two randomized controlled studies assessing its skin moisturization and barrier restoration potential, and the effect on skin microflora, Journal of Dermatological Treatment, 28:2, 173-180, DOI: 10.1080/09546634.2016 Purpose: Two randomized, intra-individual comparison studies were performed in healthy subjects to evaluate the skin moisturization and barrier restoration potential of a new topical panthenol-containing emollient (NTP-CE) (Study 1), and its effect on skin microflora (Study 2). Methods: In Study 1 (N ¼ 23), two skin areas, one challenged with 0.5% sodium dodecyl sulfate (SDS) solution and one unchallenged, were treated with NTP-CE for 3 weeks. Transepidermal water loss (TEWL), skin hydration, and intercellular lipid lamellae (ICLL) organization were measured at regular intervals during the study. In Study 2 (N ¼ 20), quantitative bacterial cultures were obtained over 6 h from a skin area undergoing wash stress with 10% SDS with subsequent single application of NTP-CE. Results: In Study 1, mean AUC for TEWL reduction from baseline was more pronounced with NTP-CE compared with control (À168.36 vs. À123.38 g/m 2 /h, p ¼ 0.023). NTP-CE use was also associated with statistically significant improvements in stratum corneum hydration and an increase in mean ICLL length from baseline (day 22: 120.61 vs. 35.85 nm/1000 nm 2 , p < 0.001). In Study 2, NTP-CE use had no negative impact on bacterial viability. Conclusions: NTP-CE use has favorable and lasting effects on barrier function and repair as well as skin hydration without negatively influencing bacterial viability. ARTICLE HISTORY

Purpose: Two studies were conducted with a new topical panthenol-containing emollient (NTP-CE) to investigate the skin-moisturizing effect in healthy adults and tolerability in healthy infants. Methods: In Study 1 (N ¼ 44), a single skin application of NTP-CE was performed followed by a 4-week twice-daily application. Skin hydration and stratum corneum (SC) water content change (using Raman spectroscopy) were measured. In the 4-week Study 2 (N ¼ 65, aged 3-25 months), NTP-CE tolerability was assessed using a 5-point scoring system; skin hydration was determined in a subset (N ¼ 21). Results: In Study 1, mean AUC 0 À 24 h for skin capacitance change from baseline was 302.03 i.u. with NTP-CE and À15.90 i.u. in control areas (p < .001). With NTP-CE (at 4 h), the water content within the upper SC part was reduced (À45.10 vs. À13.39 g/cm 2 , p ¼ .013) and the water gradient increased (0.51 vs. 0.11 g/ cm 4 , p ¼ .036), indicating relocation of water into deeper layers. In Study 2, there was no statistically significant change from baseline in mean cutaneous tolerability scores. At days 7, 14, and 28, skin hydration had increased by 42%, 54%, and 49%, respectively (all p < .001). Conclusions: Single and prolonged NTP-CE usage is associated with sustained and deep skin moisturization. NTP-CE is well tolerated by healthy infants. ARTICLE HISTORY

As an organism ages, there is a decline in mitochondrial function and cellular energy balance. This decline is both accelerated by and can cause the formation of reactive oxygen species (ROS) that damage nuclear and mitochondrial DNA, lipid membranes as well as structural and catalytic proteins, especially those involved in energetic pathways of cells. Further, ROS have also been linked to some of the detrimental skin changes that occur as a result of photoaging. We have previously shown that levels of Coenzyme Q10 (CoQ10), a component of the respiratory chain in mitochondria, are reduced in skin cells from aging donors, and that topical supplementation can ameliorate processes involved in skin aging. Creatine is another important component of the cellular energy system and phosphocreatine, its phosphorylated form, functions as a reservoir for high energy phosphates. Unfortunately the creatine system and thus the energy storage mechanism in skin are negatively affected by aging and conditions of oxidative stress. This article reviews some of our in vivo data about the synergistic effects of combining a stabilized form of Creatine with CoQ10 and clearly depicts their beneficial effects as active ingredients in topical formulations.