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

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 st em cell subsets and may influence the balance between stern cell renewal an d proliferation. Telomere length and telomerase activity was measured in wh ole blood leucocytes, neutrophils and T cells from cord blood and individua ls aged from 1 Sitar to 96 years. Rapid telomere shortening [700 base pairs (bp)] was demonstrated in the first year of life, followed by a gradual de cline of 31 bp/year. T cells were shown to have longer telomeres than neutr ophils (mean difference 372 bp, P = < 0.0011 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 haemopoiet ic cells. Stem cell utilization as measured by It chromosome inactivation p atterns was found to be independent of telomere length. This supports the c oncept that age-dependent skewed haemopoiesis is the result of random stem cell loss or X-allelic exclusion rather than telomeric senescence. These st udies provide insight into the ageing process and a reference point for eva luating replicative stress in individuals of different age groups.