The increased production of endogenous glucocorticoids (GCs) in the skin of the elderly population contributes to age-related defects strikingly similar to those occurring after pharmacologic treatments with GCs.

GCs act through the ligand-dependent transcription factors GC receptor (GR) and mineralocorticoid receptor (MR). We reported that epidermal MR plays nonredundant roles relative to GR in adult mouse skin homeostasis; however, its relative contribution to natural skin aging has not been previously investigated.

A 13-month-old MR epidermal knockout (MR^EKO) mice showed differential features of aging relative to controls (CO) in all skin compartments. MR^EKO mice were resistant to age-induced epidermal atrophy but showed reduced dermal thickness, with decreased collagen deposition and decreased SMAD2 and 3 activity. Importantly, the dermal white adipose tissue (dWAT) was 2.5-fold enlarged in 13-month MR^EKO versus CO, featuring adipocyte hyperplasia and hypertrophy at least in part through early increases in Pparg. These changes correlated with compartment-specific alterations in GC signaling. In addition, conditioned medium from MR^EKO keratinocytes increased adipocyte differentiation, indicating paracrine regulation of adipogenesis through mechanisms that include activation of β-catenin signaling. These findings highlight the importance of epidermal MR in regulating cross-talk among skin compartments in naturally aged skin through GC and β-catenin signaling pathways.

老年人皮肤中内源性糖皮质激素（GC）产量的增加，与年龄相关的缺陷非常相似，这与用GC进行药物治疗后出现的缺陷极为相似。

GC通过配体依赖性转录因子GC受体（GR）和盐皮质激素受体（MR）起作用。我们报道，在成年小鼠皮肤稳态中，表皮MR相对于GR发挥非冗余作用。但是，它对自然皮肤衰老的相对贡献尚未得到研究。

一只13个月大的MR表皮基因敲除（MR ^EKO）小鼠在所有皮肤区室中均表现出与对照组（CO）相对的衰老特征。MR ^EKO小鼠对年龄诱发的表皮萎缩具有抵抗力，但显示出真皮厚度减少，胶原蛋白沉积减少以及SMAD2和3活性降低。重要的是，在13个月的MR ^EKO中，真皮白脂肪组织（dWAT）比CO扩大了2.5倍，其特征是脂肪细胞增生和肥大至少部分是由于Pparg的早期增加。这些变化与GC信号转导中特定于隔室的变化有关。此外，MR ^EKO的条件培养基角质形成细胞增加了脂肪细胞的分化，表明旁分泌通过包括激活β-catenin信号传导的机制调节脂肪生成。这些发现凸显了表皮MR在通过GC和β-catenin信号通路调节自然衰老皮肤的皮肤隔室之间的串扰的重要性。