Normal HematopoiesisUncoupling protein 2 deficiency results in higher neutrophil counts and lower B-cell counts during aging in mice

- Uncoupling protein 2 (UCP2)-deficient bone marrow cells underwent a stronger adenosine triphosphate decline following H2O2 treatment.
- UCP2-deficient bone marrow had a larger amount of lin−Sca-1+c-kit+ (LSK) cells in young mice.
- UCP2-deficient bone marrow revealed a skewing towards myeloid cell lines throughout aging.
- UCP2-deficient bone marrow correlated with diminished erythroid cells in young and old animals.
- UCP2 deficiency was followed by significantly higher red blood cell distribution width in young and old animals.

Progress of age-related hematopoietic diseases such as myelodysplastic syndrome has previously been linked to enhanced levels of reactive oxygen species (ROS). Uncoupling protein 2 (UCP2) was found to reduce mitochondrial ROS production through uncoupling of the respiratory chain. The impact of UCP2 loss and elevated ROS on hematopoiesis during aging has not yet been investigated. In this study, UCP2 knockout mice were analyzed at aging stages of 3, 12, and 24 months with respect to oxidative and energy status of bone marrow cells. Further, the cellular bone marrow subpopulation composition was characterized, as were the differential blood counts at all time points. UCP2 knockout mice revealed enhanced levels of mitochondrial superoxide in elderly animals. Following oxidative stress, adenosine triphosphate (ATP) levels decreased more in the knockout mice than in the wild type. Investigation of bone marrow and blood counts of the knockout mice revealed an enhanced amount of monocytes and neutrophils, as well as a decreased amount of B cells and impaired erythropoiesis throughout aging. In summary, UCP2 induces protective effects on ROS and ATP levels during aging. Additionally, the results suggest an imbalance in hematopoiesis because of the lack of UCP2.