PDF(Pubmed)
Abstract：
Cellular senescence is a state of irreversible growth arrest with profound phenotypic changes, including the senescence-associated secretory phenotype (SASP). Senescent cell accumulation contributes to aging and many pathologies including chronic inflammation, type 2 diabetes, cancer, and neurodegeneration. Targeted removal of senescent cells in preclinical models promotes health and longevity, suggesting that the selective elimination of senescent cells is a promising therapeutic approach for mitigating a myriad of age-related pathologies in humans. However, moving senescence-targeting drugs (senotherapeutics) into the clinic will require therapeutic targets and biomarkers, fueled by an improved understanding of the complex and dynamic biology of senescent cell populations and their molecular profiles, as well as the mechanisms underlying the emergence and maintenance of senescence cells and the SASP. Advances in mass spectrometry-based proteomic technologies and workflows have the potential to address these needs. Here, we review the state of translational senescence research and how proteomic approaches have added to our knowledge of senescence biology to date. Further, we lay out a roadmap from fundamental biological discovery to the clinical translation of senotherapeutic approaches through the development and application of emerging proteomic technologies, including targeted and untargeted proteomic approaches, bottom-up and top-down methods, stability proteomics, and surfaceomics. These technologies are integral for probing the cellular composition and dynamics of senescent cells and, ultimately, the development of senotype-specific biomarkers and senotherapeutics (senolytics and senomorphics). This review aims to highlight emerging areas and applications of proteomics that will aid in exploring new senescent cell biology and the future translation of senotherapeutics.
摘要：
细胞衰老是一种不可逆的生长停滞状态，具有深刻的表型变化，包括衰老相关分泌表型(SASP)。衰老细胞积累有助于衰老和许多病理，包括慢性炎症，2型糖尿病,癌症,和神经变性。在临床前模型中靶向去除衰老细胞可促进健康和长寿，这表明，选择性消除衰老细胞是一种有前途的治疗方法，可以减轻人类多种与年龄相关的疾病。然而,将衰老靶向药物（senotherapeutics）转移到临床将需要治疗靶标和生物标志物，通过对衰老细胞群的复杂和动态生物学及其分子谱的理解，以及衰老细胞和SASP的出现和维持的潜在机制。基于质谱的蛋白质组学技术和工作流程的进步有可能满足这些需求。这里,我们回顾了翻译衰老研究的现状，以及迄今为止蛋白质组学方法如何增加了我们对衰老生物学的认识。Further,我们通过新兴蛋白质组学技术的开发和应用，从基础生物学发现到临床转化的方法，包括靶向和非靶向蛋白质组学方法，自下而上和自上而下的方法，稳定性蛋白质组学，和表面组学。这些技术对于探测衰老细胞的细胞组成和动力学是不可或缺的，最终,感官型特异性生物标志物和感官治疗学（感官和感官形态学）的发展。这篇综述旨在强调蛋白质组学的新兴领域和应用，这将有助于探索新的衰老细胞生物学和未来的衰老疗法的翻译。
