Erythrocyte Count, Anemia, and the Human Natural Lifespan Limit:Evidence from the Long Life Family Study

Konstantin G. Arbeev; Olivia Bagley; Joanne M. Murabito; Harvey Jay Cohen; Brandon L. Pierce; William Evan Johnson; Dan T. A. Eisenberg; Milind C. Mahajan; Stacy L. Andersen; Kaare Christensen; Joseph M. Zmuda; Bharat Thyagarajan; Sheng Luo; Anatoliy I. Yashin; Michael A. Province; Abraham Aviv

doi:10.64898/2026.06.08.730977

PhysiologybioRxivJun 26, 2026

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Erythrocyte Count, Anemia, and the Human Natural Lifespan Limit:Evidence from the Long Life Family Study

Konstantin G. Arbeev iD, Olivia Bagley, Joanne M. Murabito iD, Harvey Jay Cohen iD, Brandon L. Pierce iD, William Evan Johnson iD, Dan T. A. Eisenberg iD, Milind C. Mahajan, Stacy L. Andersen iD, Kaare Christensen iD, Joseph M. Zmuda iD, Bharat Thyagarajan iD, Sheng Luo iD, Anatoliy I. Yashin iD, Michael A. Province iD, Abraham Aviv iD

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Abstract

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 adults 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 and found that 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 emerged from modeling, independent of the World Health Organization anemia definition, which is 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 adults.