Telomere shortening and oxidative stress in aged macrophages results in impaired STAT5a phosphorylation.
Macrophages are an essential component of both innate and adaptive immunity, and altered function of these cells with aging may play a key role in immunosenescence. To determine the effect of aging on macrophages, we produced bone marrow-derived macrophages in vitro. In these conditions, we analyzed the effect of aging on macrophages without the influence of other cell types that may be affected by aging. We showed that telomeres shorten with age in macrophages leading to a decreased GM-CSF but not M-CSF-dependent proliferation of these cells as a result of decreased phosphorylation of STAT5a. Macrophages from aged mice showed increased susceptibility to oxidants and an accumulation of intracellular reactive oxygen species. In these macrophages STAT5a oxidation was reduced, which led to the decreased phosphorylation observed. Interestingly, the same cellular defects were found in macrophages from telomerase knockout (Terc(-/-)) mice suggesting that telomere loss is the cause for the enhanced oxidative stress, the reduced Stat5a oxidation and phosphorylation and, ultimately, for the impaired GM-CSF-dependent macrophage proliferation.
Sebastián
Carlos
C
Institute for Research in Biomedicine and University of Barcelona, Barcelona, Spain.
Herrero
Carmen
C
Serra
Maria
M
Lloberas
Jorge
J
Blasco
María A
MA
Celada
Antonio
A
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology*; D004249:DNA Damage / Q000276:immunology; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology*; D010766:Phosphorylation / Q000235:genetics / Q000276:immunology; D012313:RNA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase