Open AccessTelomere uncapping during in vitro T‐lymphocyte senescence
Author(s) -
Chebel Amel,
Bauwens Serge,
Gerland LucMarie,
Belleville Aurélie,
Urbanowicz Iwona,
De Climens Aude Roborel,
Tourneur Yves,
Chien Wei Wen,
Catallo Régine,
Salles Gilles,
Gilson Eric,
Ffrench Martine
Publication year - 2009
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2008.00448.x
Subject(s) - telomere , telomerase , senescence , shelterin , biology , lymphocyte , somatic cell , microbiology and biotechnology , dna damage , immunology , dna , genetics , gene , dna binding protein , transcription factor
Summary Normal lymphocytes represent examples of somatic cells that are able to induce telomerase activity when stimulated. As previously reported, we showed that, during lymphocyte long‐term culture and repeated stimulations, the appearance of senescent cells is associated with telomere shortening and a progressive drop in telomerase activity. We further showed that this shortening preferentially occured at long telomeres and was interrupted at each stimulation by a transitory increase in telomere length. In agreement with the fact that telomere uncapping triggers lymphocyte senescence, we observed an increase in γ‐H2AX and 53BP1 foci as well as in the percentage of cells exhibiting DNA damage foci in telomeres. Such a DNA damage response may be related to the continuous increase of p16 ink4a upon cell stimulation and cell aging. Remarkably, at each stimulation, the expression of shelterin genes, such as hTRF1 , hTANK1 , hTIN2 , hPOT1 and hRAP1 , was decreased. We propose that telomere dysfunction during lymphocyte senescence caused by iterative stimulations does not only result from an excessive telomere shortening, but also from a decrease in shelterin content. These observations may be relevant for T‐cell biology and aging.