DNA damage and aging on hematopoietic stem cells: Impact of oxidative stress in ApoE−/− mice

The effects of aging on ROS production and DNA damage were assessed in hematopoietic stem cells (HSCs) from apolipoprotein E–deficient (ApoE−/−) mice (2-, 12- and 24-month-old), a traditional experimental model of atherogenic dyslipidemia. HSCs from aged ApoE−/− mice were associated with increased ROS levels, leading to loss quiescence, DNA damage, apoptosis and telomere shortening. The concurrence of lack of ApoE and aging result in exhaustion and senescence of HSCs accompanied by increased oxidative stress and inflammation. Therefore, our data open avenues to a better understanding of age-related changes and genetic factors, which may synergistically compromise the efficacy of aged HSC recovery and/or transplantation. [Display omitted] •Hematopoietic stem cells exhibit the ability of differentiation into mature cells.•Hypercholesterolemia increases reactive oxygen species leading to senescence.•In aging, high cellular recruitment leads dysfunction due to oxidative stress.