Buildup from birth onward of short telomeres in human hematopoietic cells

Tsung Po Lai, Simon Verhulst, Sharon A. Savage, Shahinaz M. Gadalla, Athanase Benetos, Simon Toupance, Pam Factor-Litvak, Ezra Susser, Abraham Aviv

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Telomere length (TL) limits somatic cell replication. However, the shortest among the telomeres in each nucleus, not mean TL, is thought to induce replicative senescence. Researchers have relied on Southern blotting (SB), and techniques calibrated by SB, for precise measurements of TL in epidemiological studies. However, SB provides little information on the shortest telomeres among the 92 telomeres in the nucleus of human somatic cells. Therefore, little is known about the accumulation of short telomeres with age, or whether it limits the human lifespan. To fill this knowledge void, we used the Telomere-Shortest-Length-Assay (TeSLA), a method that tallies and measures single telomeres of all chromosomes. We charted the age-dependent buildup of short telomeres (<3 kb) in human hematopoietic cells from 334 individuals (birth-89 years) from the general population, and 18 patients with dyskeratosis congenita-telomere biology disorders (DC/TBDs), whose hematopoietic cells have presumably reached or are close to their replicative limit. For comparison, we also measured TL with SB. We found that in hematopoietic cells, the buildup of short telomeres occurs in parallel with the shortening with age of mean TL. However, the proportion of short telomeres was lower in octogenarians from the general population than in patients with DC/TBDs. At any age, mean TL was longer and the proportion of short telomeres lower in females than in males. We conclude that though converging to the TL-mediated replicative limit, hematopoietic cell telomeres are unlikely to reach this limit during the lifespan of most contemporary humans.

Original languageEnglish (US)
Article numbere13844
JournalAging cell
Volume22
Issue number6
DOIs
StatePublished - Jun 2023

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology

Keywords

  • Southern blotting
  • TeSLA
  • age
  • lifetime
  • sex
  • subtelomeric region
  • telomere biology disorders
  • telomeres
  • terminal restriction fragments

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