Why the term ‘erythrocyte aging’ is preferable to ‘erythrocyte senescence’

Over decades, nomenclature in erythrocyte cell death research has been unrefined. Recently, several attempts have been made to adapt the nomenclature suggested by the Nomenclature Committee on Cell Death (NCCD) guidelines to erythrocytes. Within the framework of the standardization of terms used in erythrocyte cell death studies, erythrocyte senescence and eryptosis, a regulated cell death of erythrocytes, have been defined and the formal distinction between both events has been recently established. Differences in their physiological role have been underscored, and markers that can be used to distinguish between erythrocyte senescence and eryptosis have been identified. As a further step, we aim to dissect cellular senescence in nucleated cells and erythrocytes, identifying their hallmarks, key triggers, molecular mechanisms, immunity-related effects, as well as physiological aspects. Available evidence suggests that cellular senescence in nucleated cells can be considered an active biological program, while erythrocyte senescence rather reflects a more passive, gradual accumulation of cellular damage. Fundamental mechanism-based and physiological differences between senescence in nucleated cells and erythrocytes highlighted in this mini-review indicate that the use of the term ‘erythrocyte senescence’ should be discouraged as misleading. Instead, the term ‘erythrocyte aging’ might be more appropriate.