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

2.50
Hdl Handle:
http://hdl.handle.net/10541/86678
Title:
Dynamics of telomere shortening in neutrophils and T lymphocytes during ageing and the relationship to skewed X chromosome inactivation patterns.
Authors:
Robertson, Jane D; Gale, Rosemary E; Wynn, Robert F; Dougal, Mark; Linch, David C; Testa, Nydia G; Chopra, Rajesh
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.
Affiliation:
Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
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
Issue Date:
May-2000
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
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorRobertson, Jane Den
dc.contributor.authorGale, Rosemary Een
dc.contributor.authorWynn, Robert Fen
dc.contributor.authorDougal, Marken
dc.contributor.authorLinch, David Cen
dc.contributor.authorTesta, Nydia Gen
dc.contributor.authorChopra, Rajeshen
dc.date.accessioned2009-11-23T11:18:09Z-
dc.date.available2009-11-23T11:18:09Z-
dc.date.issued2000-05-
dc.identifier.citationDynamics 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.en
dc.identifier.issn0007-1048-
dc.identifier.pmid10848812-
dc.identifier.doi10.1046/j.1365-2141.2000.01970.x-
dc.identifier.urihttp://hdl.handle.net/10541/86678-
dc.description.abstractHuman 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.en
dc.language.isoenen
dc.subjectHaematopoiesisen
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAging-
dc.subject.meshAnalysis of Variance-
dc.subject.meshAntigens, CD34-
dc.subject.meshChild-
dc.subject.meshChild, Preschool-
dc.subject.meshDosage Compensation, Genetic-
dc.subject.meshFetal Blood-
dc.subject.meshHematopoiesis-
dc.subject.meshHumans-
dc.subject.meshInfant-
dc.subject.meshInfant, Newborn-
dc.subject.meshLeukocytes-
dc.subject.meshLinear Models-
dc.subject.meshMiddle Aged-
dc.subject.meshNeutrophils-
dc.subject.meshT-Lymphocytes-
dc.subject.meshTelomerase-
dc.subject.meshTelomere-
dc.titleDynamics of telomere shortening in neutrophils and T lymphocytes during ageing and the relationship to skewed X chromosome inactivation patterns.en
dc.typeArticleen
dc.contributor.departmentDepartment of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.en
dc.identifier.journalBritish Journal of Haematologyen

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