Analyzing the microarray mRNA profile of graying human hair follicles: a promising approach in stress and aging research

Abstract

Regenerative medicine needs new but safe treatment approaches to balance the reported increase in stress and aging related diseases. Graying is one hallmark of aging and is associated with excessive oxidative as well as psycho-emotional stress. In graying individuals fully pigmented hair follicles are found next to white and intermediary hair follicles. Thus, young and old hair follicles are observed in parallel that share the identical genetic background. Here, we discuss data obtained by microarray analysis of 15 tissue samples, and we studied the functional relevance in the ex vivo hair follicle organ culture model. We found the expected regulation of genes responsible for pigment-production by melanocytes, the cells that generate the pigment and are gradually lost from graying hair follicles. Among the around 200 regulated gens, we also found genes associated with cellular energy metabolism (e.g. glutaminase) and with nerve fiber growth (e.g. plexin C1). These results could be confirmed on mRNA and protein level as well as by pathway-analysis. Ex vivo treatment of cultured hair follicles with l -glutamine or plexin C1 revealed biological relevance and pharmaco-interventional potential of these selected microarray-results in that these compounds were able to halt the culture-induced premature aging process and cellular stress responses (pigment production, cell proliferation, -differentiation, -apoptosis, senescence). We therefore consider the graying hair follicle a useful model to study aging and stress associated responses and report here energy metabolism and cellular plasticity as important areas for future research.