PBX1-SIRT1 Positive Feedback Loop Attenuates ROS-Mediated HF-MSC Senescence and Apoptosis

The study investigated the relationship between pre-B-cell leukemia transcription factor1 (PBX1), Silent Information Regulator 1 (SIRT1), and Poly (ADP-ribose) polymerase-1 (PARP1) in the context of hair follicle-derived mesenchymal stem cells (HF-MSCs) senescence and apoptosis. The researchers found that overexpression of PBX1 reduced senescence and apoptosis in HF-MSCs, which was associated with an increase in SIRT1 and a decrease in PARP1, as well as higher levels of intracellular NAD and ATP. Conversely, knocking down SIRT1 led to increased senescence and apoptosis, higher reactive oxygen species (ROS) accumulation, and DNA damage, along with reduced NAD and ATP levels. However, overexpressing PBX1 could rescue the negative effects of SIRT1 knockdown. The study also showed that PBX1 could counteract the ATP and NAD depletion caused by PARP1 overexpression by increasing SIRT1 expression. These findings suggest the existence of a positive feedback loop between PBX1 and SIRT1 that plays a crucial role in mitigating HF-MSCs senescence and apoptosis, offering new insights into stem cell aging and potential strategies for age-related disease prevention and treatment.