Selective ablation of primary and paracrine senescent cells by targeting iron dyshomeostasis

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 pop-ulations. 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 fer-roptosis dysregulation and ferrous iron accumulation as a common phenomenon in both primary and para-crine 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.

Automated summary

Senescent cells can spread the senescent phenotype to other cells through secretory factors. Previous characterizations of paracrine senescence were unreliable due to mixed populations of senescent and non-senescent cells. This study isolates senescent cells using DPP4 as a surface marker and enriches the percentage of paracrine senescence. The researchers observe ferroptosis dysregulation and ferrous iron accumulation in both primary and paracrine senescent cells and identify a potential senolytic approach.