Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, P.O. Box 71468-64685, Shiraz, Iran.
Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Donaueschingenstraße 13, 1200 Vienna, Austria; Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria; Institute of Molecular Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, 1190 Vienna, Austria.
Mech Ageing Dev. 2024 Feb;217:111888. doi: 10.1016/j.mad.2023.111888. Epub 2023 Nov 29.
Senescence is a cellular state characterized by its near-permanent halted cell cycle and distinct secretory phenotype. Although senescent cells have a variety of beneficial physiological functions, progressive accumulation of these cells due to aging or other conditions has been widely shown to provoke deleterious effects on the normal functioning of the same or higher-level biological organizations. Recently, erasing senescent cells in vivo, using senolytics, could ameliorate diseases identified with an elevated number of senescent cells. Since then, researchers have struggled to develop new senolytics each with different selectivity and potency. In this review, we have gathered and classified the proposed senolytics and discussed their mechanisms of action. Moreover, we highlight the heterogeneity of senolytics regarding their effect sizes, and cell type specificity as well as comment on the exploited strategies to improve these features. Finally, we suggest some prospective routes for the novel methods for ablation of senescent cells.
衰老是一种细胞状态,其特征为近乎永久的细胞周期停滞和独特的分泌表型。尽管衰老细胞具有多种有益的生理功能,但由于衰老或其他条件导致这些细胞的逐渐积累,已广泛证明会对同一或更高层次的生物组织的正常功能产生有害影响。最近,使用衰老细胞清除剂(senolytics)在体内清除衰老细胞,可以改善与衰老细胞数量增加相关的疾病。从那时起,研究人员一直在努力开发具有不同选择性和效力的新型衰老细胞清除剂。在这篇综述中,我们收集并分类了所提出的衰老细胞清除剂,并讨论了它们的作用机制。此外,我们强调了衰老细胞清除剂在作用大小、细胞类型特异性方面的异质性,并对改善这些特性所采用的策略进行了评论。最后,我们提出了一些针对衰老细胞清除的新方法的未来发展方向。