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首页> 外文期刊>The Journal of investigative dermatology. >Characterization of Skin Aging-Associated Secreted Proteins (SAASP) Produced by Dermal Fibroblasts Isolated from Intrinsically Aged Human Skin
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Characterization of Skin Aging-Associated Secreted Proteins (SAASP) Produced by Dermal Fibroblasts Isolated from Intrinsically Aged Human Skin

机译：从固有年龄的人皮肤分离的皮肤成纤维细胞产生的皮肤衰老相关分泌蛋白（SAASP）的表征

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Most molecular hallmarks of cellular senescence have been identified in studies of cells aged in vitro by driving them into replicative or stress-induced senescence. Comparatively, less is known about the characteristic features of cells that have aged in vivo. Here we provide a systematic molecular analysis of normal human dermal fibroblasts (NHDFs) that were isolated from intrinsically aged human skin of young versus middle aged versus old donors. Intrinsically aged NHDFs in culture exhibited more frequently nuclear foci positive for p53 binding protein 1 and promyelocytic leukemia protein reminiscent of 'DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS)'. Formation of such foci was neither accompanied by increased DNA double strand breaks, nor decreased cell viability, nor telomere shortening. However, it was associated with the development of a secretory phenotype, indicating incipient cell senescence. By quantitative analysis of the entire secretome present in conditioned cell culture supernatant, combined with a multiplex cytokine determination, we identified 998 proteins secreted by intrinsically aged NHDFs in culture. Seventy of these proteins exhibited an age-dependent secretion pattern and were accordingly denoted 'skin aging associated secreted proteins (SAASP)'. Systematic comparison of SAASP with the classical senescence-associated secretory phenotype (SASP) revealed that matrix degradation as well as proinflammatory processes are common aspects of both conditions. However, secretion of 27 proteins involved in the biological processes of 'metabolism' and 'adherens junction interactions' was unique for NHDFs isolated from intrinsically aged skin. In conclusion, fibroblasts isolated from intrinsically aged skin exhibit some, but not all, molecular hallmarks of cellular senescence. Most importantly, they secrete a unique pattern of proteins that is distinct from the canonical SASP and might reflect specific processes of skin aging.
机译：细胞衰老的大多数分子标志已在体外老化的细胞研究中得到了鉴定，方法是将其驱动到复制性或应激诱导的衰老过程中。相比之下，对体内已衰老的细胞的特征知之甚少。在这里，我们提供了正常人皮肤成纤维细胞（NHDFs）的系统分子分析，这些皮肤成纤维细胞是从年轻，中年和老年供体的固有年龄的人皮肤中分离出来的。在培养中固有老化的NHDFs表现出更频繁的p53结合蛋白1和早幼粒细胞白血病蛋白阳性的核灶，让人联想到“具有染色质改变增强衰老的DNA片段（DNA-SCARS）”。这种病灶的形成既不伴有增加的DNA双链断裂，也不伴有细胞活力的降低，也没有端粒的缩短。然而，它与分泌表型的发展有关，表明初期细胞衰老。通过定量分析条件细胞培养上清液中存在的整个分泌组，并结合多重细胞因子测定，我们鉴定了由培养物中固有老化的NHDF分泌的998种蛋白质。这些蛋白质中有70种表现出年龄依赖性的分泌模式，因此被称为“皮肤衰老相关分泌蛋白（SAASP）”。 SAASP与经典的衰老相关分泌表型（SASP）的系统比较表明，基质降解以及促炎过程是这两种情况的共同方面。然而，从固有老化的皮肤中分离出的NHDFs分泌涉及“代谢”和“粘附连接相互作用”这一生物学过程的27种蛋白质。总之，从本质上老化的皮肤中分离出的成纤维细胞表现出一些但不是全部的细胞衰老的分子标志。最重要的是，它们分泌出独特的蛋白质模式，该蛋白质模式不同于典型的SASP，并且可能反映皮肤衰老的特定过程。

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