Project description:Quiescent adult muscle stem cells (MuSCs) regenerate skeletal muscle upon injury throughout life. However, aged skeletal muscles fail to maintain stem cell quiescence, leading to declines in MuSC number and functionality. Although autophagy plays an important role in the maintenance of MuSC quiescence, how quiescent MuSCs and their autophagy levels are maintained throughout life is largely unknown. The current study reveals how GnRH, a hypothalamic hormone, maintains the quiescence of adult MuSCs by preventing the onset of senescence and how the decline of sex steroids in organismal ageing is implicated in MuSC ageing.
Project description:Activation of mostly quiescent hematopoietic stem cells (HSC) is a prerequisite for life-long blood production1, 2. This process requires major molecular adaptations to meet the regulatory and metabolic requirements for cell division3-8. The mechanisms governing cellular reprograming upon stem cell activation and their subsequent return to quiescence are still not fully characterized. Here, we describe a role for chaperone-mediated autophagy (CMA)9, a selective form of lysosomal protein degradation, in sustaining adult HSC function. CMA is required for stem cell protein quality control and upregulation of fatty acid metabolism upon HSC activation. We identify that CMA activity decreases with age in HSC and show that genetic or pharmacological activation of CMA can restore functionality of old HSC. Together, our findings provide mechanistic insights into a new role for CMA in sustaining quality control, appropriate energetics and overall long-term hematopoietic stem cell function. Our work supports that CMA may be a promising therapeutic target to enhance hematopoietic stem cell function in conditions such as aging or stem cell transplantation.
Project description:Phenotypic and functional changes seen in the aged adaptive immune system are primarily driven by aging of hematopoietic stem cells (HSCs), pharmacological rejuvenated aged HSCs were able to reconstituted a youthful immune system
