The Journal of Experimental Medicine
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J. Exp. Med., Volume 190, Number 2, July 19, 1999 157-168
Copyright © 1999 by The Rockefeller University Press.

Telomere Fluorescence Measurements in Granulocytes and T Lymphocyte Subsets Point to a High Turnover of Hematopoietic Stem Cells and Memory T Cells in Early Childhood

Nathalie Rufera, Tim H. Brümmendorfa, Steen Kolvraab, Claus Bischoffb, Kaare Christensenc, Louis Wadsworthd,e, Michael Schulzere,f, and Peter M. Lansdorpa,e
a From the Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada
b Institute of Human Genetics, University of Aarhus, 8000 Aarhus, Denmark
c Institute of Public Health, Epidemiology, Odense University Medical School, DK-5000 Odense C, Denmark
d Department of Pathology, BC Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada
e Department of Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada
f Department of Statistics, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada

Correspondence to: Peter M. Lansdorp, Terry Fox Laboratory, 601 West 10th Ave., Vancouver, BC V5Z 1L3, Canada., peter{at}terryfox.ubc.ca (E-mail), 604-877-6070, ext. 3026 (phone), 604-877-0712 (fax)

To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and flow cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.

Key Words: telomere length dynamics, telomere length inheritance, cellular turnover, immune senescence, stem cell self-renewal


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