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Preliminary — 34/100 Other bioRxiv

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

biorxiv (preprint) 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.
TL;DR

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 (

Credibility Assessment Preliminary — 34/100
Study Design
Rigor of the research methodology
5/20
Sample Size
Whether the study was sufficiently powered
7/20
Peer Review
Review status and journal reputation
4/20
Replication
Has this finding been independently reproduced?
6/20
Transparency
Funding disclosure and data availability
12/20
Overall
Sum of all five dimensions
34/100

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.

Regulatory
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