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Telomerase, a RNA-dependent DNA polymerase that adds telomeric DNA at the 3' ends of eukaryotic chromosomes, is essential for the lifelong preservation of the proliferative potential of antigen specific T lymphocytes. However, senescent T cells that have low telomerase activity, short telomeres and lack of replicative capacity accumulate in old humans, patients with chronic viral infections and cancer. The mechanisms inhibiting telomerase in these cells are poorly understood. Here I describe a strategy that was successfully applied to identify pathways causing telomerase dysfunction in primary human senescent T lymphocytes. Such strategy couples lentiviral vector-based gene manipulations to functional and signaling readouts directly ex vivo, in humans.

Original publication




Journal article


Methods mol biol

Publication Date





119 - 126


AMP-responsive-protein kinase, Intra-sensory signaling, Senescence, T cells, Telomerase, Cell Proliferation, Cellular Senescence, Humans, Molecular Biology, Neoplasms, T-Lymphocytes, Telomerase, Telomere