SENS Research Foundation, Mountain View, CA 94041, USA.
SENS Research Foundation, Mountain View, CA 94041, USA.
Cell Rep. 2023 Feb 28;42(2):112058. doi: 10.1016/j.celrep.2023.112058. Epub 2023 Feb 6.
Senescent cells can spread the senescent phenotype to other cells by secreting senescence-associated secretory phenotype factors. The resulting paracrine senescent cells make a significant contribution to the burden of senescent cell accumulation with age. Previous efforts made to characterize paracrine senescence are unreliable due to analyses being based on mixed populations of senescent and non-senescent cells. Here, we use dipeptidyl peptidase-4 (DPP4) as a surface maker to isolate senescent cells from mixed populations. Using this technique, we enrich the percentage of paracrine senescence from 40% to 85%. We then use this enriched culture to characterize DPP4 primary and paracrine senescent cells. We observe ferroptosis dysregulation and ferrous iron accumulation as a common phenomenon in both primary and paracrine senescent cells. Finally, we identify ferroptosis induction and ferrous iron-activatable prodrug as a broad-spectrum senolytic approach to ablate multiple types of primary and paracrine senescent cells.
衰老细胞可以通过分泌衰老相关分泌表型因子将衰老表型传播给其他细胞。由此产生的旁分泌衰老细胞对衰老细胞积累的负担有很大贡献。由于之前对旁分泌衰老的分析是基于衰老和非衰老细胞的混合群体,因此这些努力的结果并不可靠。在这里,我们使用二肽基肽酶-4(DPP4)作为表面标记物从混合群体中分离衰老细胞。使用这项技术,我们将旁分泌衰老的比例从 40%富集到 85%。然后,我们使用这种富集培养物来表征 DPP4 原代和旁分泌衰老细胞。我们观察到铁死亡失调和亚铁积累是原代和旁分泌衰老细胞的共同现象。最后,我们确定铁死亡诱导和亚铁激活前药是一种广谱的衰老细胞溶解剂,可清除多种类型的原代和旁分泌衰老细胞。
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