P8.109 Mechanisms of endogenous skin aging

E. Makrantonaki, S. Fimmel, H. Seltmann, C.E. Orfanos, Ch.C. Zouboulis

Department of Dermatology, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany

Skin aging is a complex biological phenomenon. While molecular mechanisms of exogenous skin aging have been thoroughly studied, knowledge on endogenous skin aging and the role of hormonal deficiency on it has remained limited. Serum levels of hormones decline with age in female and male individuals. Systemic substitution with estradiol in females and growth hormone (GH) in males has led to inhibition of the skin aging process in single controlled studies. To understand the molecular mechanisms of endogenous skin aging and the influence of hormones we developed an in vitro model using human skin cells maintained at hormone-substituted defined conditions, which correspond to average serum levels for females and males from 0 to 60 years (y) of life. Three hours in culture represented one year of life, whereas hormone levels were kept unchanged at the level of 20 y in control experiments. Receptors for GH, insulin, IGF-I, androgens, and estrogens were examined by highly sensitive RT-PCR and Western blotting in SZ95 sebocytes, epidermal keratinocytes  and dermal fibroblasts and were found to be overall expressed but at different levels in each cell type. The receptor expression levels were partially regulated by their ligands. SZ95 sebocytes incubated with hormones at aged female levels (60 y) showed significantly lower content of neutral lipids (-84%; nile red lipid microassay), whereas fibroblasts showed decreased proliferation. Parallelly increased mRNA levels of genes associated with aging signs such as c-myc (+63%) and fibronectin (+48%) measured by Northern blotting were detected compared to those detected in cells at 20-y female hormone levels after a 5-day treatment. Polar lipids, cell proliferation, and cell toxicity remained unchanged. In conclusion, hormone- induced skin aging has a significant effect on the proliferation, the lipid production of skin cells and the expression of certain genes. Moreover, these experiments may serve as models for identification of aging-associated endocrine mechanisms and pathways and may also facilitate studies of molecular aging mechanisms in the future.