186 JOURNAL OF COSMETIC SCIENCE Trans-cutaneous penetration studies have shown that this new biovector induces a very good penetration of active compounds inside the deep part of the skin, which is a property particularly interesting for substances developed for instance for their ability to promote extracellular matrix synthesis, or to inhibit MMPs or tyrosinase activities. Moreover, for the active compounds that have been tested during these studies, penetrations were far above the ones obtained with standard liposomes, which makes those fluidic nanoparticles very interesting for their cosmetic activities. Observations of those nanoparticules were also performed into suspension using fluorescent microscopy (Axioskop2+, Zeiss), with a rhodamine filter (546/590), after encapsulation of Octadecyl Rhodamine (Molecular probes, USA). The particle size last from 100 to 300 nm according to the nature of the active compound that is encapsulated. The stability of size and shape has been controlled into suspension for more than 2 years. Mathematical modelisation was performed using advanced modelisation computer models using Turbo-Frodo software and docking experiments to evaluate the complex hybrid structure organisation of such capsule membranes. Encapsulation of different active compounds performed: vitamins (B6, B3, H, B12, B2, A and E), slimming products such as caffeine, theophyllin, carnitine, and Centella Asiatica extract: antioxidants such as ubiquinones and whitening products such as catechol or lipoic acid. Conclusion and penpeetives These new tluidic and fractal nanosized vectors allow an improved performance of encapsulated active compounds devoted for the deeper part of the skin, without providing any side effect. It is a safe biovector, and allows some real breakthrough in the Nanotechnology field that induces a complete modification in the usual classification of nano-biovectors. The next evolution of those biovectors will be around cell targeting, which could be made by grafting some chemical structures with cell membrane affinities, onto the structure of those nanoparticles

2005 ANNUAL SCIENTIFIC MEETING 187 SIRTl, THE HUMAN HOMOLOGUE TO SIR2, IS EXPRESS:ED :IN HUMAN SKIN AND IN CULTURED KERATINOCYTES FIBROBLASTS AND HaCaT CELLS AND ITS LEVEL IS CLOSELY RELATED TO STRESS AND AGING Claude Dal Farra, Ph.D. and N. Domloge Vincience Research Center, Sophia Antipolis, France Introduction The SIR2 (silent infonnation regulator 2) gene family was first studied in yeast, and it is a family of protein deacetylases (Sirtuins) that are NAD(+)-dependent enzymes. Evidence progressively showed that SIR2, a NAD-dependent histone deacetylase, is the founding member of the family of sirtuins. Studies in yeast have shown that the SIR2 family has diverse biological functions including gene silencing, DNA repair, cell cycle progression, development, metabolism, apoptosis, heterochromatin fonnation, and aging.1-6 The discovery that SIR2 requires NAD for its activity immediately suggested a link between SIR2 activity and caloric restriction. This link was strengthened by the observation that life span extension by caloric restriction requires the SIR2 protein.7-IO The discovery that overexpression of SIR2 is sufficient to extend life span in yeast elevated SIR2 to the central position of aging research in this organism. In mammalian cells, studies have identified SIRTl as the homologue of the Saccharomyces cerevisiae chromatin silencing factor SIR2. In the studies that followed, 4 types of human SIRT were identified. SIRTl has been found to associate with the tumor suppressor protein p53, and the deacetylation ofp53 by SIRTl has been shown to negatively regulate p53-mediated transcription. Therefore, the role ofSIRTl in preventing cellular senescence and apoptosis induced by DNA damage and stress has been strongly suggested. Hence, it is becoming increasingly apparent that SIRTl is a key regulator of cell defense and cell survival in response to stress. Results Immunostaining studies of cultured human keratinocytes, HaCaT cells and fibroblasts demonstrated that SIRTl exhibits a clear nuclear staining in these cells. Irnmunofluorescence studies showed that, with low doses ofUVB stress, SIRTl expression increases in a dose-dependent manner, while p53 expression shows very little variation. In contrast, at higher UV doses (above 40-50m.J/cm2) SIRTl expression decreases while p53 expression increases significantly. SIRTl expression in human fibroblasts exposed to different low UVB doses pSJ expression In human fibroblasts exposed to different low UVB doses Control cdls (A), cells irradiated with 15 mJICJ111 (B), 50 ,,,J/cm1 (CJ, and 75 mJlcm2 (D) This result corroborates SIRT's role in the protection of cells by suppressing p53 after a moderate injury of cells by UVB after stronger, damaging UV doses, p53 takes over, leading the cell to cell cycle arrest or apoptosis. mRNA studies confumed this finding and showed that SIRTl mRNA increased 3 h after low doses of UVB and lasted for 24 h. In response to caloric restriction, SIRTl expression increased, in a dose-dependent manner, to reach maximum expression with total glucose deprivation (for 24 and 48 h), while p53 levels varied very little under these conditions.