905 Sex differences in the molecular cause of perioral skin wrinkling

Abstract

Wrinkling is the hallmark of skin aging. We have previously reported that perioral wrinkling is more severe in females; however the molecular basis for this is unknown. We enrolled 12 subjects (n=6 male/female) age 54-86 with Griffith’s photoaging severity grade between 4 and 8 (0=none, 8=severe) and took biopsies from both the perioral and periocular region. Using qPCR, we assessed RNA expression levels of collagen I, collagen III, cysteine-rich angiogenic inducer 61 (CYR61), and insulin like growth factor 1 (IGF-1). CYR61 causes dermal fibroblast senescence in response to photodamage, leading to the decreased collagen production linked to skin wrinkling. IGF-1 is produced by dermal fibroblasts and plays a role in regulating the hair cycle and promoting oxidative stress. While there was no difference between females’ and males’ Griffith’s grade (6.67 and 5.67 respectively, p=0.096) or periocular wrinkling grade (3.2 and 2.6 respectively, p=0.421), females did have a significantly more severe perioral wrinkling grade when compared with males (6.2 and 2.8 respectively, p=.0.035). Consistent with the increase in severity in perioral wrinkling, females also expressed significantly more CYR61 (p=0.018) than males, however, they also expressed more collagen III (p=0.016). In this location, there was no significant difference in collagen I (p=0.115) or IGF-1 (p=0.124) expression between males and females, although females trended towards higher expression of both, with the latter marker’s role in oxidative stress potentially contributing to the increased perioral wrinkling in females. In the periocular region, there were no significant differences between males and females in the expression levels of all four markers. While both sexes had similar overall photoaging and gene expression in the periocular region, the perioral region expressed significant molecular differences between the sexes, which may contribute to the greater perioral skin wrinkling seen clinically in females. It also highlights the complex process of skin aging and the influence of specific anatomic milieu in this process.