History Stem cells of intensely regenerative tissues are susceptible to cellular damage. (2- 12 and 24-month-old respectively) C57BL/6?J AHU-377 mice. Results Aged HSCs showed an increase in intracellular superoxide anion (1.4-fold) hydrogen peroxide (2-fold) nitric oxide (1.6-fold) peroxynitrite/hidroxil (2.6-fold) compared with young cells. We found that mitochondria and NADPHox AHU-377 were the major sources of ROS production in the three groups studied whereas CYP450 contributed in middle and aged and xanthine oxidase only in aged HSCs. In addition we observed DNA damage and apoptosis in the middle (4.2- and 2-fold respectively) and aged (6- and 4-fold respectively) mice; aged mice also exhibited a significantly shorter telomere length (?1.8-fold) AHU-377 and a lower expression of plasticity markers. Conclusion These data suggest that aging impairs the functionality of HSCs and that these age-associated alterations may affect the efficacy of aged HSC recovery and transplantation. <0 .05 (*) level. Results Aging stimulates cell cycling and myeloid skewing To evaluate the impact of aging on HSCs (KTLS/CD133+) we decided the number of cells and proliferation by cell cycle analysis (Table?1) and complete blood count (CBC) (Table?2). We observed a 3.3-fold increase in the number of HSCs during the lifespan (p?p?p?AHU-377 in HSCs in the three sets of pets. As BPTP3 illustrated in the very best -panel and summarized in the club graphs of Fig.?1 we observed a clear age-related increase in ROS production. Specifically our data showed significant increases in the levels of ?O2? and NO only in aged HSCs (1.4- and 1.6-fold respectively) and augmentation in the H2O2 and in the hROS levels in both middle (1.2- 1.4 respectively) and aged (2- 2.6 respectively) compared with young HSCs (p?