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    Dynamics of telomere shortening in neutrophils and T lymphocytes during ageing and the relationship to skewed X chromosome inactivation patterns.

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    Authors
    Robertson, Jane D
    Gale, Rosemary E
    Wynn, Robert F
    Dougal, Mark
    Linch, David C
    Testa, Nydia G
    Chopra, Rajesh
    Affiliation
    Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
    Issue Date
    2000-05
    
    Metadata
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    Abstract
    Human haemopoiesis undergoes profound changes throughout life, resulting in compromised regenerative capacity of haemopoietic stem cells. It has been suggested that telomere shortening results in senescence of haemopoietic stem cell subsets and may influence the balance between stem cell renewal and proliferation. Telomere length and telomerase activity was measured in whole blood leucocytes, neutrophils and T cells from cord blood and individuals aged from 1 year to 96 years. Rapid telomere shortening [700 base pairs (bp)] was demonstrated in the first year of life, followed by a gradual decline of 31 bp/year. T cells were shown to have longer telomeres than neutrophils (mean difference 372 bp, P = < 0.001) but demonstrated similar rates of shortening (20 +/- 0.3 bp/year vs. 22 +/- 0.3 bp/year). Telomerase was detectable in T cells but not in neutrophils, suggesting that telomerase is not the rate-limiting step for regulation of telomere length in haemopoietic cells. Stem cell utilization as measured by X chromosome inactivation patterns was found to be independent of telomere length. This supports the concept that age-dependent skewed haemopoiesis is the result of random stem cell loss or X-allelic exclusion rather than telomeric senescence. These studies provide insight into the ageing process and a reference point for evaluating replicative stress in individuals of different age groups.
    Citation
    Dynamics of telomere shortening in neutrophils and T lymphocytes during ageing and the relationship to skewed X chromosome inactivation patterns. 2000, 109 (2):272-9 Br. J. Haematol.
    Journal
    British Journal of Haematology
    URI
    http://hdl.handle.net/10541/86678
    DOI
    10.1046/j.1365-2141.2000.01970.x
    PubMed ID
    10848812
    Type
    Article
    Language
    en
    ISSN
    0007-1048
    ae974a485f413a2113503eed53cd6c53
    10.1046/j.1365-2141.2000.01970.x
    Scopus Count
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