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

Admasu, Tesfahun Dessale, Kim, Kristie, Rae, Michael, Avelar, Roberto ORCID: 0000-0003-4997-9953, Gonciarz, Ryan L, Rebbaa, Abdelhadi, Magalhaes, Joao Pedro de, Renslo, Adam R, Stolzing, Alexandra and Sharma, Amit
(2023) Selective ablation of primary and paracrine senescent cells by targeting iron dyshomeostasis. CELL REPORTS, 42 (2). 112058-.

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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<sup>+</sup> 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.

Item Type: Article
Uncontrolled Keywords: Iron, Phenotype, Dipeptidyl Peptidase 4, Cellular Senescence
Divisions: Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 21 Feb 2023 15:39
Last Modified: 07 Oct 2023 10:21
DOI: 10.1016/j.celrep.2023.112058
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