Abstract
Although some prior studies have identified an association between exposure to fine air-borne particulate matter (PM2.5) and indices of aging, the extent of these associations and their underlying mechanisms are uncertain. In this study, we exposed male C57BL/6J mice to filtered air and concentrated ambient PM2.5 (CAP) and assessed 2 common hallmarks of aging, telomere shortening and a senescent phenotype. Of the cell types examined, peripheral blood mononuclear cells (PBMNCs), endothelial progenitor cells (EPCs), and bone marrow-derived c-kit+ cells, all 3 demonstrated shortened telomeres when isolated from CAP-exposed mice as compared with cells derived from filtered air controls. We found that telomere attrition in PBMNCs and EPCs was mitigated in those CAP-exposed mice receiving water supplemented with the antioxidant, carnosine, and was reversible in PBMNCs, but not EPCs, when CAP-exposed mice were allowed to recover in normal air conditions. Telomere attrition in these cell types appeared to result from the attenuated catalytic activity of telomerase reverse transcriptase (Tert). PBMNCs and EPCs obtained from CAP-exposed mice also displayed increased β-galactosidase activity and expression of genes characteristic of the senescence-activated secretory phenotype. Of PBMNC subtypes, the increase of β-galactosidase activity was greatest in CD8+ T-cells. Our results suggest that the pro-aging effects of PM2.5 impact multiple cell types, including bone marrow stem cells, and that telomere attrition resulted from attenuated Tert activity. The aging and senescence of multiple cell types, including bone marrow stem cells, may underlie the diverse pathological outcomes of PM2.5 exposure.