RESUMEN
The goal of our work has been to investigate the mechanisms of gender-independent human skin ageing and examine the hypothesis of skin being an adequate model of global ageing. For this purpose, whole genome gene profiling was employed in sun-protected skin obtained from European Caucasian young and elderly females (mean age 26.7±4 years [n1â=â7] and 70.75±3.3 years [n2â=â4], respectively) and males (mean age 25.8±5.2 years [n3â=â6] and 76±3.8 years [n4â=â7], respectively) using the Illumina array platform. Confirmation of gene regulation was performed by real-time RT-PCR and immunohistochemistry. 523 genes were significantly regulated in female skin and 401 genes in male skin for the chosen criteria. Of these, 183 genes exhibited increased and 340 decreased expression in females whereas 210 genes showed increased and 191 decreased expression in males with age. In total, 39 genes were common in the target lists of significant regulated genes in males and females. 35 of these genes showed increased (16) or decreased (19) expression independent of gender. Only 4 overlapping genes (OR52N2, F6FR1OP2, TUBAL3 and STK40) showed differential regulation with age. Interestingly, Wnt signalling pathway showed to be significantly downregulated in aged skin with decreased gene and protein expression for males and females, accordingly. In addition, several genes involved in central nervous system (CNS) ageing (f.i. APP, TAU) showed to be expressed in human skin and were significanlty regulated with age. In conclusion, our study provides biomarkers of endogenous human skin ageing in both genders and highlight the role of Wnt signalling in this process. Furthermore, our data give evidence that skin could be used as a good alternative to understand ageing of different tissues such as CNS.
Asunto(s)
Envejecimiento/genética , Envejecimiento de la Piel/genética , Transcriptoma , Vía de Señalización Wnt/genética , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Envejecimiento/efectos de la radiación , Biomarcadores/metabolismo , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/efectos de la radiación , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de la radiación , Estudio de Asociación del Genoma Completo , Humanos , Inmunohistoquímica , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores Sexuales , Envejecimiento de la Piel/efectos de la radiación , Luz Solar , Rayos Ultravioleta , Vía de Señalización Wnt/efectos de la radiaciónRESUMEN
BACKGROUND AND OBJECTIVE: Skin, being a mirror of the body, is a major target for aging research. Aging is a complex process that involves the decline of function or dysfunction of many systems. The corticotropin-releasing hormone (CRH) system is involved in skin inflammation. In addition, CRH has a suggested role in age-associated conditions and in animal aging models. However, a consistent logic interaction between the different CRH system components and the aging process has, to our knowledge, never been examined before. METHODS: The expression of CRH, CRH-binding protein (CRHBP), CRH receptor 1 (CRHR1), and CRH receptor 2 (CRHR2) in healthy skin samples of 42 patients of different ages (18-92 years) was evaluated by immunohistochemistry, and the age-related changes were assessed. RESULTS: Compared with young skin, the aged skin displayed an upregulation of CRH in sebaceous glands and CRHR1 in hair follicles and the epidermis. Moreover, age-associated downregulation of CRHBP in the sebaceous and sweat glands was detected, whereas the CRHR2 showed no age-related changes. CONCLUSION: Our findings suggest that the age-associated changes in the expression of CRH system components reflect an exaggerated stress response reaction, putting the aged skin continuously in a stress-like situation.
