Red Blood Cells and Human Aging: Exploring Their Biomarker Potential.

Aging is a complex biological process marked by progressive physiological decline with increasing vulnerability to diseases such as cardiovascular disorders, neurodegenerative conditions, and metabolic syndromes. Identifying reliable biomarkers of aging is essential for assessing biological age, predicting health outcomes, and guiding interventions to promote healthy aging. Among various candidate biomarkers, red blood cells (RBCs) offer a unique and accessible window into the aging process due to their abundance, finite lifespan, and responsiveness to systemic changes. This review examines the potential of RBCs as biomarkers of aging by exploring their age-associated morphological, functional, and biochemical alterations. Age-related reduction in key haematological parameters such as RBC count, haemoglobin concentration, and haematocrit, and increases in mean cell volume (MCV) and red cell distribution width (RDW), reflect underlying shifts in erythropoiesis and cellular turnover. Functional changes include reduced oxygen-carrying capacity, decreased deformability, diminished ATP release, and increased RBC aggregation, all of which may impair both macrocirculatory and microcirculatory flow and tissue oxygenation. Biochemically, aging RBCs exhibit altered membrane lipid and protein composition, reduced membrane fluidity, and diminished antioxidant and enzymatic activity, contributing to cellular senescence and clearance. Despite these promising indicators, challenges persist in establishing RBC parameters as definitive biomarkers of aging. Inter-individual and intra-individual variability and storage-related artifacts complicate their use. In conclusion, RBCs present a compelling, though currently underutilized, avenue for aging biomarker research. Further longitudinal validation and mechanistic research are essential to support the clinical utility of RBC parameters as biomarkers of aging.