The senescence-associated secretory phenotype (SASP) has recently emerged as a driver of and promising therapeutic target for multiple age-related conditions, ranging from neurodegeneration to cancer. The complexity of the SASP, typically assessed by a few dozen secreted proteins, has been greatly underestimated, and a small set of factors cannot explain the diverse phenotypes it produces in vivo. Here, we present the "SASP Atlas," a comprehensive proteomic database of soluble proteins and exosomal cargo SASP factors originating from multiple senescence inducers and cell types. Each profile consists of hundreds of largely distinct proteins but also includes a subset of proteins elevated in all SASPs. Our analyses identify several candidate biomarkers of cellular senescence that overlap with aging markers in human plasma, including Growth/differentiation factor 15 (GDF15), stanniocalcin 1 (STC1), and serine protease inhibitors (SERPINs), which significantly correlated with age in plasma from a human cohort, the Baltimore Longitudinal Study of Aging (BLSA). Our findings will facilitate the identification of proteins characteristic of senescence-associated phenotypes and catalog potential senescence biomarkers to assess the burden, originating stimulus, and tissue of origin of senescent cells in vivo.

中文翻译：

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衰老生物标记物发育的蛋白质组图谱与衰老相关的分泌蛋白。

衰老相关的分泌表型（SASP）最近已成为多种年龄相关疾病（从神经变性到癌症）的驱动者和有希望的治疗靶标。SASP的复杂性（通常由几十种分泌的蛋白质评估）已被大大低估了，一小部分因素无法解释其在体内产生的多种表型。在这里，我们介绍“ SASP Atlas”，这是一个由多种衰老诱导物和细胞类型引起的可溶性蛋白质和外泌体SASP因子的综合蛋白质组学数据库。每个图谱由数百种截然不同的蛋白质组成，但也包括所有SASP中升高的一部分蛋白质。我们的分析确定了与人类血浆中的衰老标记重叠的几种细胞衰老的生物标记，包括巴尔的摩纵向老龄化研究（BLSA），包括生长/分化因子15（GDF15），锡骨钙素1（STC1）和丝氨酸蛋白酶抑制剂（SERPIN），它们与人类人群血浆中的年龄显着相关。我们的发现将有助于鉴定与衰老相关的表型的蛋白质，并分类潜在的衰老生物标志物，以评估体内衰老细胞的负担，起源刺激和起源组织。