Examining the effects of reactive oxygen species on functional potential of HSCS during aging
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The role of ROS in the hematopoietic system has been a subject that has received little investigation due to the hypoxic environment inherent in the bone marrow niche. Furthermore, it is not known whether or not oxidative damage accumulations play a role in the functional decline of HSCs associated with aging. Measuring DNA damage and ROS levels using the Fragment Length Analysis by Repair Enzyme (FLARE) assay, I show here that there are indeed significantly detectable levels of 8-oxoguanine, a lesion associated with ROS, present in both young and old murine HSCs. In an attempt to attenuate the presence of these lesions, a four-week treatment with the thiol-based antioxidant N-Acetyl-L-Cysteine was administered orally to mice. Analysis revealed significant decreases in oxidative lesions in both the young and old HSC compartment. Additionally, it was demonstrated that the NAC treatment significantly reduced number of baseline DNA breaks in old, but not young, HSCs. Together these results suggest that DNA damage accumulation is a dynamic process that changes as cells age. Further understanding of the role of ROS will help elucidate the importance of this type of DNA damage on the declining functional potential associated with aging.