The "telomereless" erythrocytes and telomere-length dependent erythropoiesis

Abstract

Approximately 25 trillion erythrocytes (red blood cells) circulate in the bloodstream of an adult human, surpassing the number of circulating leukocytes (white blood cells) by a factor of about 1000. Moreover, the erythrocyte turnover rate accounts for approximately 76% of the turnover rate of all circulating blood cells. This simple math shows that the hematopoietic system principally spends its telomere length-dependent replicative capacity on building and maintaining the erythrocyte blood pool. Erythropoiesis (red blood cell production) is thus the principal cause of telomere shortening with age in hematopoietic cells (HCs), a conclusion that holds significant implications for linking telomere length dynamics in HCs to health and lifespan of modern humans.

Keywords: aging; anemia; biomarker; erythropoiesis; hematopoiesis; leukocytes.

FIGURE 1

The hematopoietic hierarchy. Hematopoietic stem cells (HSCs) are at the top of the hierarchy and unipotent progenitor cells (UPCs) are at the bottom. No entry sign denotes hematopoietic cells that have reached replicative senescence, prompting signaling for increased replication of cells up the hierarchy.

FIGURE 2

Cell proportions and daily cellular turnovers in the soma and blood of a normal adult. The top panel draws on data from reference Sender et al.,  (left), and complete blood cell count with differential (https://www.bowtie.com.hk/blog/en/full‐blood‐count/) (right). Values in the bottom panel are expressed as the percentage of total somatic cell turnover, drawing on data from reference Sender & Milo,  (left), and data rescaled from somatic cell turnovers (right).