Hematologic analysis is an efficient and valuable tool for real-time health monitoring and immune analysis in mouse aging studies. However, many frequently used blood sampling techniques in mice are incompatible with continuous monitoring with increasing age, as they may involve anesthesia, cause severe stress, or require a high volume of blood. This technical report describes a convenient relatively noninvasive procedure for counting white blood cells in C57Bl/6 mice by an optimized tail blood collection method followed by Wright-Giemsa and Türk staining. This technique can be performed on unanesthetized mice in less than 1 min with minimal stress using only a few microliters of blood. White blood cell analysis can include but is not limited to total and differential white blood cell count and cell morphology. The low blood volume collected is ideal for aging mice in longer-term experiments requiring regular and continuous monitoring.

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The ability to respond to stress, defined as resilience, was measured by white blood cell counts in C57BL/6 mice of various ages receiving a nonlethal dose of cyclophosphamide (CYP). Neutrophil counts dipped and then rebounded in a consistent and age-dependent manner. Low neutrophil rebound correlated with improved learning in middle-age mice suggesting CYP-nduced neutrophil response may predict resilience to aging. Keywords: Resilience to aging, wound healing, ear punch biopsy, aging mice