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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2023-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/79196 |
| _version_ | 1797905556454768640 |
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| author | Patryk Slusarczyk Pratik Kumar Mandal Gabriela Zurawska Marta Niklewicz Komal Chouhan Raghunandan Mahadeva Aneta Jończy Matylda Macias Aleksandra Szybinska Magdalena Cybulska-Lubak Olga Krawczyk Sylwia Herman Michal Mikula Remigiusz Serwa Małgorzata Lenartowicz Wojciech Pokrzywa Katarzyna Mleczko-Sanecka |
| author_facet | Patryk Slusarczyk Pratik Kumar Mandal Gabriela Zurawska Marta Niklewicz Komal Chouhan Raghunandan Mahadeva Aneta Jończy Matylda Macias Aleksandra Szybinska Magdalena Cybulska-Lubak Olga Krawczyk Sylwia Herman Michal Mikula Remigiusz Serwa Małgorzata Lenartowicz Wojciech Pokrzywa Katarzyna Mleczko-Sanecka |
| author_sort | Patryk Slusarczyk |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-10T10:07:12Z |
| format | Article |
| id | doaj.art-d6c8686415fe4090aee6edece8741fc1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-10T10:07:12Z |
| publishDate | 2023-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-d6c8686415fe4090aee6edece8741fc12023-02-15T16:39:43ZengeLife Sciences Publications LtdeLife2050-084X2023-01-011210.7554/eLife.79196Impaired iron recycling from erythrocytes is an early hallmark of agingPatryk Slusarczyk0https://orcid.org/0000-0003-2383-3630Pratik Kumar Mandal1https://orcid.org/0000-0002-1566-5641Gabriela Zurawska2https://orcid.org/0000-0003-1465-8957Marta Niklewicz3https://orcid.org/0000-0002-3407-795XKomal Chouhan4https://orcid.org/0000-0003-4769-8787Raghunandan Mahadeva5https://orcid.org/0000-0001-5865-6430Aneta Jończy6https://orcid.org/0000-0002-4333-6853Matylda Macias7Aleksandra Szybinska8Magdalena Cybulska-Lubak9https://orcid.org/0000-0002-1029-3156Olga Krawczyk10Sylwia Herman11https://orcid.org/0000-0001-9750-0746Michal Mikula12https://orcid.org/0000-0003-3447-7328Remigiusz Serwa13https://orcid.org/0000-0002-4684-3754Małgorzata Lenartowicz14https://orcid.org/0000-0003-4714-0783Wojciech Pokrzywa15https://orcid.org/0000-0002-5110-4462Katarzyna Mleczko-Sanecka16https://orcid.org/0000-0001-9095-9597International Institute of Molecular and Cell Biology in Warsaw, Warsaw, PolandInternational Institute of Molecular and Cell Biology in Warsaw, Warsaw, PolandInternational Institute of Molecular and Cell Biology in Warsaw, Warsaw, PolandInternational Institute of Molecular and Cell Biology in Warsaw, Warsaw, PolandInternational Institute of Molecular and Cell Biology in Warsaw, Warsaw, PolandInternational Institute of Molecular and Cell Biology in Warsaw, Warsaw, PolandInternational Institute of Molecular and Cell Biology in Warsaw, Warsaw, PolandInternational Institute of Molecular and Cell Biology in Warsaw, Warsaw, PolandInternational Institute of Molecular and Cell Biology in Warsaw, Warsaw, PolandMaria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandMaria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandLaboratory of Genetics and Evolution, Institute of Zoology and Biomedical Research, Jagiellonian University, Cracow, PolandMaria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandIMol Polish Academy of Sciences, Warsaw, Poland; ReMedy International Research Agenda Unit, IMol Polish Academy of Sciences, Warsaw, PolandLaboratory of Genetics and Evolution, Institute of Zoology and Biomedical Research, Jagiellonian University, Cracow, PolandInternational Institute of Molecular and Cell Biology in Warsaw, Warsaw, PolandInternational Institute of Molecular and Cell Biology in Warsaw, Warsaw, PolandAging 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.https://elifesciences.org/articles/79196hepcidinferroportinproteostasis |
| spellingShingle | Patryk Slusarczyk Pratik Kumar Mandal Gabriela Zurawska Marta Niklewicz Komal Chouhan Raghunandan Mahadeva Aneta Jończy Matylda Macias Aleksandra Szybinska Magdalena Cybulska-Lubak Olga Krawczyk Sylwia Herman Michal Mikula Remigiusz Serwa Małgorzata Lenartowicz Wojciech Pokrzywa Katarzyna Mleczko-Sanecka Impaired iron recycling from erythrocytes is an early hallmark of aging eLife hepcidin ferroportin proteostasis |
| 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 | hepcidin ferroportin proteostasis |
| url | https://elifesciences.org/articles/79196 |
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