TY - JOUR
T1 - Buildup from birth onward of short telomeres in human hematopoietic cells
AU - Lai, Tsung Po
AU - Verhulst, Simon
AU - Savage, Sharon A.
AU - Gadalla, Shahinaz M.
AU - Benetos, Athanase
AU - Toupance, Simon
AU - Factor-Litvak, Pam
AU - Susser, Ezra
AU - Aviv, Abraham
N1 - Funding Information: T‐PL's telomere research is supported by the National Institutes of Health U01AG066529 and New Jersey Alliance for Clinical and Translational Science Career Development Award NJACTS KL2 TR003018. SS' and SG's research is funded in part by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute. AB's research is supported by the French National Research Agency (ANR), Translationnelle: N°ID RCB: 2014‐A00298‐39: 2014–2017 and partially supported by the French PIA project “Lorraine Université d'Excellence” reference ANR‐15‐IDEX‐04‐LUE, and the Investments for the Future program under grant agreement no. ANR‐15‐RHU‐0004. ST's is supported by the French PIA project “Lorraine Université d'Excellence” reference ANR‐15‐IDEX‐04‐LUE; FHU project CARTAGE‐PROFILES (Aviesan, 2021–2025); French National Research Agency (ANR), Translationnelle: N°ID RCB: 2014‐A00298‐39. ClinicalTrials.gov Unique Identifiers: NCT02176941(TELARTA) and NCT01391442 (STANISLAS). PF‐L's is funded by the following National Institutes of Health grants: R01 HD071180 from the National Institute of Child Health and Development and R21 ES023582 and 5P30 ES009089 from the National Institute of Environmental Health Sciences. Funded by the National Institutes of Health (NIH). AA's telomere research is supported by the National Institutes of Health (grants R01HD071180 and U01AG066529) and a grant from the Norwegian Research Council (ES562296). Publisher Copyright: © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - Southern blotting
KW - TeSLA
KW - age
KW - lifetime
KW - sex
KW - subtelomeric region
KW - telomere biology disorders
KW - telomeres
KW - terminal restriction fragments
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U2 - https://doi.org/10.1111/acel.13844
DO - https://doi.org/10.1111/acel.13844
M3 - Article
C2 - 37118904
SN - 1474-9718
VL - 22
JO - Aging cell
JF - Aging cell
IS - 6
M1 - e13844
ER -