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Selective ablation of primary and paracrine senescent cells by targeting iron dyshomeostasis
journal contribution
posted on 2023-02-17, 15:39 authored by Tesfahun Dessale Admasu, Kristie Kim, Michael Rae, Roberto Avelar, Ryan L Gonciarz, Abdelhadi Rebbaa, João Pedro de Magalhães, Adam R Renslo, Alexandra StolzingAlexandra Stolzing, Amit SharmaSenescent 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.
Funding
SENS Research Foundation (SRF) grant ID: SRF20190200P1
History
School
- Mechanical, Electrical and Manufacturing Engineering
Published in
Cell ReportsVolume
42Issue
2Publisher
ElsevierVersion
- VoR (Version of Record)
Rights holder
© The AuthorsPublisher statement
This is an Open Access Article. It is published by Elsevier under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (CC BY-NC-ND). Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/Acceptance date
2023-01-17Publication date
2023-02-06Copyright date
2023ISSN
2211-1247Publisher version
Language
- en