Role of Telomere In Human Lymphocyte Function and Aging

National Institute On Aging

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Abstract

Telomere and telomerase are key factors that regulate cell replicative lifespan. Telomere shortening has been observed in many types of cells in vitro and in cross-sectional analyses, and significantly shortened telomeres induce cell senescence and apoptosis. However, it remains to be determined how telomere length change in vivo and whether dysfunctional shortened telomeres contribute to age-associated decline of function. To address these questions, we conducted a longitudinal analysis of lymphocyte subset composition, telomere length and telomerase expression in peripheral blood lymphocytes and monocytes over 100 old individuals (mean starting age 82, over 5 years time). As expected, we observed some known age-associated changes, such as increase of 1) CD8+CD28-CD45RA+ cells, 2) Treg cells (CD4+CD25+Foxp3+), and 3) monocytes and NK cells in the older donors but not young donors. Interestingly, changes of telomere length are dynamic in vivo: over half of donors showed a various degree of telomere loss while less than one-third of donors had no detectable loss of telomere in PBMC, lymphocytes and monocytes. Furthermore, despite of a great degree of difference of induced telomerase activity among donors, levels of induced telomerase activity appeared to quite stable in both T and B cells for an given individual over 5 year time. Together, these findings demonstrated for the first time that the rates of telomere attrition and the levels of induced telomerase activity in blood lymphocytes in vivo differ significantly among old individuals. The physiological significance of the rates of telomere attrition, the absolute length of telomeres, and the levels of telomerase activity in lymphocytes in the overall immune function as well as factors that influence the rates of telomere attrition and telomerase expression are under current investigation.