Reactive oxygen species contribute to dysfunction of bone marrow hematopoietic stem cells in aged C57BL/6 J mice.
BACKGROUND
Stem cells of intensely regenerative tissues are susceptible to cellular damage. Although the response to this process in hematopoietic stem cells (HSCs) is crucial, the mechanisms by which hematopoietic homeostasis is sustained are not completely understood. Aging increases reactive oxygen species (ROS) levels and inflammation, which contribute to increased proliferation, senescence and/or apoptosis, leading to self-renewal premature exhaustion. In this study, we assessed ROS production, DNA damage, apoptosis, senescence and plasticity in young, middle and aged (2-, 12- and 24-month-old, respectively) C57BL/6 J 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 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) and a lower expression of plasticity markers.


CONCLUSIONS
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.
Laboratory of Translational Physiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, Brazil. cella.porto@gmail.com.
Marcella L
ML
Porto
Laboratory of Translational Physiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, Brazil. biancarodrigues02@hotmail.com.
Bianca P
BP
Rodrigues
Laboratory of Translational Physiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, Brazil. thiagonmenezes@gmail.com.
Thiago N
TN
Menezes
Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, Brazil. saraceschim@gmail.com.
Sara L
SL
Ceschim
Nephrology Division, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, SP, Brazil. casarini.elena@unifesp.br.
Dulce E
DE
Casarini
Division of Nephrology, McMaster University, Hamilton, ON, Canada. agatagava@hotmail.com.
Agata L
AL
Gava
Laboratory of Translational Physiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, Brazil. pereiratmc@gmail.com.|Federal Institute of Education, Science and Technology, Vila Velha, ES, Brazil. pereiratmc@gmail.com.
Thiago Melo C
TM
Pereira
Laboratory of Translational Physiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, Brazil. evasquez@pq.cnpq.br.|Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, Brazil. evasquez@pq.cnpq.br.
Elisardo C
EC
Vasquez
Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, Brazil. biancacampagnaro@yahoo.com.br.
Bianca P
BP
Campagnaro
Laboratory of Translational Physiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, Brazil. smeyrelles@pq.cnpq.br.
Silvana S
SS
Meyrelles
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D016922:Cellular Senescence; D004249:DNA Damage; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species