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Impaired iron recycling from erythrocytes is an early hallmark of aging

Aging affects iron homeostasis, as evidenced by tissue iron loading and anemia in the elderly. Iron needs in mammals are met primarily by iron recycling from senescent red blood cells (RBCs), a task chiefly accomplished by splenic red pulp macrophages (RPMs) via erythrophagocytosis. Given that RPMs...

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Autores principales: Slusarczyk, Patryk, Mandal, Pratik Kumar, Zurawska, Gabriela, Niklewicz, Marta, Chouhan, Komal, Mahadeva, Raghunandan, Jończy, Aneta, Macias, Matylda, Szybinska, Aleksandra, Cybulska-Lubak, Magdalena, Krawczyk, Olga, Herman, Sylwia, Mikula, Michal, Serwa, Remigiusz, Lenartowicz, Małgorzata, Pokrzywa, Wojciech, Mleczko-Sanecka, Katarzyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931393/
https://www.ncbi.nlm.nih.gov/pubmed/36719185
http://dx.doi.org/10.7554/eLife.79196
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author Slusarczyk, Patryk
Mandal, Pratik Kumar
Zurawska, Gabriela
Niklewicz, Marta
Chouhan, Komal
Mahadeva, Raghunandan
Jończy, Aneta
Macias, Matylda
Szybinska, Aleksandra
Cybulska-Lubak, Magdalena
Krawczyk, Olga
Herman, Sylwia
Mikula, Michal
Serwa, Remigiusz
Lenartowicz, Małgorzata
Pokrzywa, Wojciech
Mleczko-Sanecka, Katarzyna
author_facet Slusarczyk, Patryk
Mandal, Pratik Kumar
Zurawska, Gabriela
Niklewicz, Marta
Chouhan, Komal
Mahadeva, Raghunandan
Jończy, Aneta
Macias, Matylda
Szybinska, Aleksandra
Cybulska-Lubak, Magdalena
Krawczyk, Olga
Herman, Sylwia
Mikula, Michal
Serwa, Remigiusz
Lenartowicz, Małgorzata
Pokrzywa, Wojciech
Mleczko-Sanecka, Katarzyna
author_sort Slusarczyk, Patryk
collection PubMed
description Aging affects iron homeostasis, as evidenced by tissue iron loading and anemia in the elderly. Iron needs in mammals are met primarily by iron recycling from senescent red blood cells (RBCs), a task chiefly accomplished by splenic red pulp macrophages (RPMs) via erythrophagocytosis. Given that RPMs continuously process iron, their cellular functions might be susceptible to age-dependent decline, a possibility that has been unexplored to date. Here, we found that 10- to 11-month-old female mice exhibit iron loading in RPMs, largely attributable to a drop in iron exporter ferroportin, which diminishes their erythrophagocytosis capacity and lysosomal activity. Furthermore, we identified a loss of RPMs during aging, underlain by the combination of proteotoxic stress and iron-dependent cell death resembling ferroptosis. These impairments lead to the retention of senescent hemolytic RBCs in the spleen, and the formation of undegradable iron- and heme-rich extracellular protein aggregates, likely derived from ferroptotic RPMs. We further found that feeding mice an iron-reduced diet alleviates iron accumulation in RPMs, enhances their ability to clear erythrocytes, and reduces damage. Consequently, this diet ameliorates hemolysis of splenic RBCs and reduces the burden of protein aggregates, mildly increasing serum iron availability in aging mice. Taken together, we identified RPM collapse as an early hallmark of aging and demonstrated that dietary iron reduction improves iron turnover efficacy.
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spelling pubmed-99313932023-02-16 Impaired iron recycling from erythrocytes is an early hallmark of aging Slusarczyk, Patryk Mandal, Pratik Kumar Zurawska, Gabriela Niklewicz, Marta Chouhan, Komal Mahadeva, Raghunandan Jończy, Aneta Macias, Matylda Szybinska, Aleksandra Cybulska-Lubak, Magdalena Krawczyk, Olga Herman, Sylwia Mikula, Michal Serwa, Remigiusz Lenartowicz, Małgorzata Pokrzywa, Wojciech Mleczko-Sanecka, Katarzyna eLife Cell Biology Aging affects iron homeostasis, as evidenced by tissue iron loading and anemia in the elderly. Iron needs in mammals are met primarily by iron recycling from senescent red blood cells (RBCs), a task chiefly accomplished by splenic red pulp macrophages (RPMs) via erythrophagocytosis. Given that RPMs continuously process iron, their cellular functions might be susceptible to age-dependent decline, a possibility that has been unexplored to date. Here, we found that 10- to 11-month-old female mice exhibit iron loading in RPMs, largely attributable to a drop in iron exporter ferroportin, which diminishes their erythrophagocytosis capacity and lysosomal activity. Furthermore, we identified a loss of RPMs during aging, underlain by the combination of proteotoxic stress and iron-dependent cell death resembling ferroptosis. These impairments lead to the retention of senescent hemolytic RBCs in the spleen, and the formation of undegradable iron- and heme-rich extracellular protein aggregates, likely derived from ferroptotic RPMs. We further found that feeding mice an iron-reduced diet alleviates iron accumulation in RPMs, enhances their ability to clear erythrocytes, and reduces damage. Consequently, this diet ameliorates hemolysis of splenic RBCs and reduces the burden of protein aggregates, mildly increasing serum iron availability in aging mice. Taken together, we identified RPM collapse as an early hallmark of aging and demonstrated that dietary iron reduction improves iron turnover efficacy. eLife Sciences Publications, Ltd 2023-01-31 /pmc/articles/PMC9931393/ /pubmed/36719185 http://dx.doi.org/10.7554/eLife.79196 Text en © 2023, Slusarczyk, Mandal et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Slusarczyk, Patryk
Mandal, Pratik Kumar
Zurawska, Gabriela
Niklewicz, Marta
Chouhan, Komal
Mahadeva, Raghunandan
Jończy, Aneta
Macias, Matylda
Szybinska, Aleksandra
Cybulska-Lubak, Magdalena
Krawczyk, Olga
Herman, Sylwia
Mikula, Michal
Serwa, Remigiusz
Lenartowicz, Małgorzata
Pokrzywa, Wojciech
Mleczko-Sanecka, Katarzyna
Impaired iron recycling from erythrocytes is an early hallmark of aging
title Impaired iron recycling from erythrocytes is an early hallmark of aging
title_full Impaired iron recycling from erythrocytes is an early hallmark of aging
title_fullStr Impaired iron recycling from erythrocytes is an early hallmark of aging
title_full_unstemmed Impaired iron recycling from erythrocytes is an early hallmark of aging
title_short Impaired iron recycling from erythrocytes is an early hallmark of aging
title_sort impaired iron recycling from erythrocytes is an early hallmark of aging
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931393/
https://www.ncbi.nlm.nih.gov/pubmed/36719185
http://dx.doi.org/10.7554/eLife.79196
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