Systematic and Cell Type-Specific Telomere Length Changes in Subsets of Lymphocytes

Abstract

Telomeres, the protective DNA-protein complexes at the ends of linear chromosomes, are important for genome stability. Leukocyte or peripheral blood mononuclear cell (PBMC) telomere length is a potential biomarker for human aging that integrates genetic, environmental, and lifestyle factors and is associated with mortality and risks for major diseases. However, only a limited number of studies have examined longitudinal changes of telomere length and few have reported data on sorted circulating immune cells. We examined the average telomere length (TL) in CD4+, CD8+CD28+, and CD8+CD28- T cells, B cells, and PBMCs, cross-sectionally and longitudinally, in a cohort of premenopausal women. We report that TL changes over 18 months were correlated among these three T cell types within the same participant. Additionally, PBMC TL change was also correlated with those of all three T cell types, and B cells. The rate of shortening for B cells was significantly greater than for the three T cell types. CD8+CD28- cells, despite having the shortest TL, showed significantly more rapid attrition when compared to CD8+CD28+ T cells. These results suggest systematically coordinated, yet cell type-specific responses to factors and pathways contribute to telomere length regulation.

Figure 1

Telomere length in sorted cells and PBMCs. Box and whisker plots display interquartile range, median values, and maximum and minimum values. Telomere length is expressed as basepairs as described earlier [19]. (a) Telomere length in B cells, CD4+, CD8+CD28+, and CD8+CD28− T cells, and PBMCs at base visit and 18 month visit. (b) Telomere length of the base visit and that of 18-month visit from the same cell type of the same individual are highly correlated. The graph includes telomere length from PBMC, CD4+, CD8+CD28+, and CD8+CD28− T cells and B cells from 39 subjects. (c) Telomere length change from base visit to 18 months is negatively correlated with telomere length at base visit. (d) Telomere length change from base visit to 18 months in total PBMC, CD4+, CD8+CD28+, and CD8+CD28− T cells and B cells. N = 39 for each cell type.

Figure 2

Box and whisker plots display interquartile range, median values, and maximum and minimum values of telomerase activity in B cells, CD4+, CD8+CD28+, and CD8+CD28− T cells, and PBMCs.