The potential of erythrocytes as cellular aging models

Kaestner, Lars; Minetti, Giampaolo

doi:10.1038/cdd.2017.100

Cited by 52 publications

(42 citation statements)

References 17 publications

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“…We have recently supported with novel experimental evidence the old notion that maturation and aging of circulating RBCs also require an intervention of the spleen (Ciana et al, 2017a , b ; Kaestner and Minetti, 2017 ). In short, we have observed a disproportionate loss of flotillin-2 with respect to the loss in surface area that occurs during the ageing in vivo of normal human RBCs (approximately −17%).…”

Section: Discussionsupporting

confidence: 54%

Continuous Change in Membrane and Membrane-Skeleton Organization During Development From Proerythroblast to Senescent Red Blood Cell

et al. 2018

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Within the context of erythropoiesis and the possibility of producing artificial red blood cells (RBCs) in vitro, a most critical step is the final differentiation of enucleated erythroblasts, or reticulocytes, to a fully mature biconcave discocyte, the RBC. Reviewed here is the current knowledge about this fundamental maturational process. By combining literature data with our own experimental evidence we propose that the early phase in the maturation of reticulocytes to RBCs is driven by a membrane raft-based mechanism for the sorting of disposable membrane proteins, mostly the no longer needed transferrin receptor (TfR), to the multivesicular endosome (MVE) as cargo of intraluminal vesicles that are subsequently exocytosed as exosomes, consistently with the seminal and original observation of Johnstone and collaborators of more than 30 years ago (Pan BT, Johnstone RM. Cell. 1983;33:967-978). According to a strikingly selective sorting process, the TfR becomes cargo destined to exocytosis while other molecules, including the most abundant RBC transmembrane protein, band 3, are completely retained in the cell membrane. It is also proposed that while this process could be operating in the early maturational steps in the bone marrow, additional mechanism(s) must be at play for the final removal of the excess reticulocyte membrane that is observed to occur in the circulation. This processing will most likely require the intervention of the spleen, whose function is also necessary for the continuous remodeling of the RBC membrane all along this cell's circulatory life.

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Section: Discussionsupporting

confidence: 54%

Continuous Change in Membrane and Membrane-Skeleton Organization During Development From Proerythroblast to Senescent Red Blood Cell

et al. 2018

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“…Along similar lines, the NCCD discourages the use of the term eryptosis, which has been coined to indicate the demise of erythrocytes exposed to stress [ 1031 ]. Irrespectively of the unquestionable relevance of this process for human pathophysiology [ 1032 – 1034 ], it is indeed extremely complex from a conceptual standpoint to define the death of entities that—in physiological conditions—exist in a debatable state between life and death (such as erythrocytes and viruses).…”

Section: Non-lethal Processesmentioning

confidence: 99%

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

et al. 2018

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Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

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“…Furthermore, it is well known that there is an age-dependent increase of the protein ratio of band 4.1a:4.1b proteins, which is regarded as a molecular clock. Measurements of the 4.1a:4.1b ratio make it possible to determine differences in cell age of erythrocytes separated in fractions (Mueller et al, 1987;Inaba and Maede, 1988;Kaestner and Minetti, 2017).…”

Section: Introductionmentioning

confidence: 99%

Intracellular Ca2+ Concentration and Phosphatidylserine Exposure in Healthy Human Erythrocytes in Dependence on in vivo Cell Age

et al. 2020

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After about 120 days of circulation in the blood stream, erythrocytes are cleared by macrophages in the spleen and the liver. The "eat me" signal of this event is thought to be the translocation of phosphatidylserine from the inner to the outer membrane leaflet due to activation of the scramblase, while the flippase is inactivated. Both processes are triggered by an increased intracellular Ca 2+ concentration. Although this is not the only mechanism involved in erythrocyte clearance, in this minireview, we focus on the following questions: Is the intracellular-free Ca 2+ concentration and hence phosphatidylserine exposure dependent on the erythrocyte age, i.e. is the Ca 2+ concentration, progressively raising during the erythrocyte aging in vivo? Can putative differences in intracellular Ca 2+ and exposure of phosphatidylserine to the outer membrane leaflet be measured in age separated cell populations? Literature research revealed less than dozen of such publications with vastly contradicting results for the Ca 2+ concentrations but consistency for a lack of change for the phosphatidylserine exposure. Additionally, we performed reanalysis of published data resulting in an ostensive illustration of the situation described above. Relating these results to erythrocyte physiology and biochemistry, we can conclude that the variation of the intracellular free Ca 2+ concentration is limited with 10 μM as the upper level of the concentration. Furthermore, we propose the hypothesis that variations in measured Ca 2+ concentrations may to a large extent depend on the experimental conditions applied but reflect a putatively changed Ca 2+ susceptibility of erythrocytes in dependence of in vivo cell age.

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The potential of erythrocytes as cellular aging models

Cited by 52 publications

References 17 publications

Continuous Change in Membrane and Membrane-Skeleton Organization During Development From Proerythroblast to Senescent Red Blood Cell

Continuous Change in Membrane and Membrane-Skeleton Organization During Development From Proerythroblast to Senescent Red Blood Cell

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

Intracellular Ca2+ Concentration and Phosphatidylserine Exposure in Healthy Human Erythrocytes in Dependence on in vivo Cell Age

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