ABSTRACT

Introduction

Cellular senescence is a rapidly growing field with potential relevance for the treatment of multiple human diseases. In the last decade, cellular senescence and the senescence-associated secretory phenotype (SASP) have emerged as central drivers of aging and many chronic diseases, including cancer, neurodegeneration, heart disease and osteoarthritis. Major efforts are underway to develop drugs that selectively eliminate senescent cells (senolytics) or alter the SASP (senomorphics) to treat age-related diseases in humans. The translation of senescence-targeting therapies into humans is still in early stages. Nonetheless, it is clear that proteomic approaches will facilitate the discovery of important SASP proteins, development of senescence- and SASP-derived biomarkers, and identification of therapeutic targets for senolytic and senomorphic drugs.

Areas covered

We review recent proteomic studies of cellular senescence and their translational relevance and, particularly, characterization of the secretory phenotype and preclinical development of biomarkers (from 2008–2020, PubMed). We focus on emerging areas, such as the heterogeneity of senescent cells and the SASP, extracellular vesicles released by senescent cells, and validating biomarkers of aging in vivo.

Expert opinion

Proteomic and multi-omic approaches will be important for the development of senescence-based biomarkers to facilitate and monitor future therapeutic interventions that target senescent cells.

中文翻译：

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蛋白质组学监测衰老相关的分泌表型及以后的能力：应用于临床。

摘要

介绍

细胞衰老是一个快速发展的领域，与多种人类疾病的治疗具有潜在的相关性。在过去的十年中，细胞衰老和与衰老相关的分泌表型（SASP）已成为衰老和许多慢性疾病（包括癌症，神经退行性疾病，心脏病和骨关节炎）的主要驱动力。目前正在进行重大努力，以开发可选择性消除衰老细胞（senolytics）或改变SASP（senomorphics）的药物来治疗人类与年龄相关的疾病。靶向衰老的疗法向人类的转化仍处于早期阶段。尽管如此，很明显，蛋白质组学方法将促进重要SASP蛋白的发现，衰老和SASP衍生生物标记的开发以及对Senolytic和Senomorphic药物的治疗靶标的识别。

覆盖区域

我们回顾了细胞衰老及其翻译相关性的最新蛋白质组学研究，尤其是分泌表型的表征和生物标志物的临床前开发（从2008年至2020年，PubMed）。我们专注于新兴领域，例如衰老细胞和SASP的异质性，衰老细胞释放的细胞外囊泡，以及验证体内衰老的生物标志物。

专家意见

蛋白质组学和多组学方法对于开发基于衰老的生物标记物以促进和监测针对衰老细胞的未来治疗性干预措施将至关重要。