Erythropoiesis is the most replication-intensive process in the body. Its lifelong replicative demands may erode hematopoietic cells' replicative capacity, leading to a decline in erythrocyte count (EC) in older individuals and limiting their lifespan. We examined the relationship between EC and mortality among 1,620 participants aged [≥]70 years in the Long Life Family Study, among whom lower EC further augmented the exponential age-dependent rise in mortality. We identified an EC threshold (ECT) (~3.8x1012/L) below which mortality was amplified (p=9.3x10-6). As EC declined with age (p=8.2x10-18), it fell below this threshold in many participants, sharply increasing their mortality risk. This mortality-based ECT in older individuals emerged from modeling, independent of the WHO anemia definition based on statistical thresholds (5th centiles) of hemoglobin distribution in populations [≤] 65 years. Thus, declining EC may be one of the biological factors imposing a natural lifespan limit on many older individuals.
Arbeev, K. G., Bagley, O., Murabito, J. M., Cohen, H. J., Pierce, B. L., Johnson, W. E., Eisenberg, D. T. A., Mahajan, M. C., Andersen, S. L., Christensen, K., Zmuda, J. M., Thyagarajan, B., Luo, S., Yashin, A. I., Province, M. A., Aviv, A.
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