There is growing evidence that the appearance and texture of the skin that is altered during the aging process are considerably enhanced by the accumulation of senescent dermal fibroblasts. These senescent cells magnify aging via an inflammatory, histolytic, and senescence-associated secretory phenotype (SASP). Secreted frizzled-related protein 4 (SFRP4) was previously determined to be expressed in dermal fibroblasts of aging skin, and its increased expression has been shown to promote cellular senescence. However, its role in the SASP remains unknown. We found that SFRP4 was significantly expressed in p16ink4a-positive human skin fibroblasts and that treatment with recombinant SFRP4 promoted SASP and senescence, whereas siRNA knockdown of SFRP4 suppressed SASP. Furthermore, we found that knockdown of SFRP4 in mouse skin ameliorates age-related reduction of subcutaneous adipose tissue, panniculus carnosus muscle layer, and thinning and dispersion of collagen fibers. These findings suggest a potential candidate for the development of new skin rejuvenation therapies that suppress SASP.

中文翻译：

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通过敲低分泌的卷曲相关蛋白 4 下调衰老相关分泌表型有助于预防皮肤老化

越来越多的证据表明，衰老过程中发生改变的皮肤外观和质地因衰老真皮成纤维细胞的积累而显着增强。这些衰老细胞通过炎症、组织溶解和衰老相关分泌表型 (SASP) 放大衰老。分泌的卷曲相关蛋白 4 (SFRP4) 先前被确定在老化皮肤的真皮成纤维细胞中表达，其表达增加已被证明可促进细胞衰老。然而，它在 SASP 中的作用仍然未知。我们发现 SFRP4 在 p16ink4a 阳性人皮肤成纤维细胞中显着表达，并且重组 SFRP4 的处理促进了 SASP 和衰老，而 SFRP4 的 siRNA 敲低抑制了 SASP。此外，我们发现小鼠皮肤中 SFRP4 的敲低改善了与年龄相关的皮下脂肪组织、肉膜层肌肉层以及胶原纤维变薄和分散的减少。这些发现提示了开发抑制 SASP 的新皮肤再生疗法的潜在候选者。