The current understanding of skin aging is that senescent fibroblasts accumulate within the dermis and subcutaneous fat to cause abnormal tissue remodeling and extracellular matrix dysfunction, triggering a senescence-associated secretory phenotype (SASP). A novel therapeutic approach to prevent skin aging is to specifically eliminate senescent dermal fibroblasts; this requires the identification of specific protein markers for senescent cells. Apolipoprotein D (ApoD) is involved in lipid metabolism and antioxidant responses and is abundantly expressed in tissues affected by age-related diseases such as Alzheimer's disease and atherosclerosis. However, its behavior and role in skin aging remain unclear. In this study, we examined whether ApoD functions as a marker of aging using human dermal fibroblast aging models. In cellular senescence models induced via replicative aging and ionizing radiation exposure, ApoD expression was upregulated at the gene and protein levels and correlated with senescence-associated β-galactosidase activity and the decreased uptake of the proliferation marker BrdU, which was concomitant with the upregulation of SASP genes. Furthermore, ApoD-positive cells were found to be more abundant in the aging human dermis using fluorescence flow cytometry. These results suggest that ApoD is a potential clinical marker for identifying aging dermal fibroblasts.

中文翻译：

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鉴定载脂蛋白 D 作为人类衰老真皮成纤维细胞标志物以开发嫩肤疗法

目前对皮肤老化的理解是，衰老的成纤维细胞在真皮和皮下脂肪内积聚，引起异常的组织重塑和细胞外基质功能障碍，引发衰老相关分泌表型（SASP）。一种防止皮肤老化的新治疗方法是专门消除衰老的真皮成纤维细胞；这需要鉴定衰老细胞的特定蛋白质标记。载脂蛋白 D (ApoD) 参与脂质代谢和抗氧化反应，并在受年龄相关疾病（如阿尔茨海默病和动脉粥样硬化）影响的组织中大量表达。然而，其在皮肤老化中的行为和作用仍不清楚。在这项研究中，我们使用人类真皮成纤维细胞老化模型检查了 ApoD 是否作为老化标志物发挥作用。在通过复制老化和电离辐射暴露诱导的细胞衰老模型中，ApoD 表达在基因和蛋白质水平上调，并与衰老相关的 β-半乳糖苷酶活性和增殖标记 BrdU 的摄取减少相关，这伴随着SASP 基因。此外，使用荧光流式细胞术发现 ApoD 阳性细胞在老化的人类真皮中更为丰富。这些结果表明 ApoD 是识别老化真皮成纤维细胞的潜在临床标志物。这伴随着 SASP 基因的上调。此外，使用荧光流式细胞术发现 ApoD 阳性细胞在老化的人类真皮中更为丰富。这些结果表明 ApoD 是识别老化真皮成纤维细胞的潜在临床标志物。这伴随着 SASP 基因的上调。此外，使用荧光流式细胞术发现 ApoD 阳性细胞在老化的人类真皮中更为丰富。这些结果表明 ApoD 是识别老化真皮成纤维细胞的潜在临床标志物。