Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance.
Telomeres are the DNA-protein complexes that protect the ends of eukaryotic chromosomes. The cellular enzyme telomerase counteracts telomere shortening by adding telomeric DNA. A growing body of literature links shorter telomere length and lower telomerase activity with various age-related diseases and earlier mortality. Thus, leukocyte telomere length (LTL) and telomerase activity are emerging both as biomarkers and contributing factors for age-related diseases. However, no clinical study has directly examined telomerase activity and telomere length in different lymphocyte subtypes isolated from the same donors, which could offer insight into the summary measure of leukocyte telomere maintenance. We report the first quantitative data in humans examining both levels of telomerase activity and telomere length in four lymphocyte subpopulations from the same donors-CD4+, CD8+CD28+ and CD8+CD28- T cells and B cells, as well as total PBMCs-in a cohort of healthy women. We found that B cells had the highest telomerase activity and longest telomere length; CD4+ T cells had slightly higher telomerase activity than CD8+CD28+ T cells, and similar telomere length. Consistent with earlier reports that CD8+CD28- T cells are replicatively senescent cells, they had the lowest telomerase activity and shortest telomere length. In addition, a higher percentage of CD8+CD28- T cells correlated with shorter total PBMC TL (r=-0.26, p=0.05). Interestingly, telomerase activities of CD4+ and CD8+CD28+ T cells from the same individual were strongly correlated (r=0.55, r<0.001), indicating possible common mechanisms for telomerase activity regulation in these two cell subtypes. These data will facilitate the understanding of leukocyte aging and its relationship to human health.
Lin
Jue
J
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, United States. jue.lin@ucsf.edu
Epel
Elissa
E
Cheon
Joshua
J
Kroenke
Candyce
C
Sinclair
Elizabeth
E
Bigos
Marty
M
Wolkowitz
Owen
O
Mellon
Synthia
S
Blackburn
Elizabeth
E
D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood / Q000502:physiology*; D015703:Antigens, CD / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure; D015415:Biomarkers / Q000032:analysis*; D015331:Cohort Studies; D004247:DNA / Q000032:analysis*; D005260:Female; D006801:Humans; D016131:Lymphocyte Subsets / Q000502:physiology* / Q000648:ultrastructure; D008875:Middle Aged; D013601:T-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure; D019098:Telomerase / Q000276:immunology / Q000378:metabolism*; D016615:Telomere / Q000502:physiology / Q000648:ultrastructure*
D015703:Antigens, CD; D015415:Biomarkers; D004247:DNA; D019098:Telomerase