Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism

摘要: Telomerase reverse transcriptase (TERT) contributes to the prevention of aging by a largely unknown mechanism that is unrelated telomere lengthening. The current study used ataxia-telangiectasia mutated (ATM) and TERT doubly deficient mice evaluate contributions 2 aging-regulating molecules, ATM, process. ATM demonstrated increased progression had shorter lifespans than ATM-null mice, while alone was insufficient affect lifespan. ATM-TERT null show in vivo senescence, especially hematopoietic tissues, dependent on p16(INK4a) p19(ARF), but not p21. As their HSCs decreased stem cell activities, accelerated seen these has been attributed impaired function. TERT-deficient are characterized reactive oxygen species (ROS) fragility, which suggested cause impairment during aging, apoptotic markedly mice. p38MAPK activation indicated be partially involved ROS-induced apoptosis TERT-null HSCs, BCL-2 provide part protective mechanisms TERT. demonstrates mitigates protecting under stressful conditions through length-independent mechanisms.