Title: The Secret to Youthful Hematopoietic Stem Cells: The Role of Cyclophilin A in Maintaining Regenerative Potential and Averting Aging
Hematopoietic stem cells (HSCs) are known for their ability to remain dormant in the bone marrow while continuously replenishing blood cells, thereby maintaining a relatively youthful profile throughout an organism’s life. Researchers from Baylor College of Medicine have discovered the crucial role of the enzyme cyclophilin A in HSCs’ longevity and regenerative potential.
Aging is often associated with the accumulation of damaged proteins that can disrupt cell function. According to Dr. André Catic, corresponding author, “Cells that frequently divide can dispose of protein aggregates through dilution. However, long-lived HSCs face the problem of the accumulation of misfolded proteins and subsequent toxic stress.”
Co-first author Dr. Lauren Maneix added, “Understanding the molecular mechanisms that contribute to HSC aging has significant clinical relevance for cancer treatment.”
The study, published in Nature Cell Biology, reveals that cyclophilin A, a molecular chaperone and one of the most abundant chaperones in mammalian cells, is a key factor in HSC longevity. By preserving and altering the three-dimensional conformation of existing proteins, molecular chaperones play a vital role in the aging process.
Cyclophilin A was found to be prevalent in HSCs and essential for maintaining the structural diversity of proteins in the cells. The research indicates that genetic depletion of cyclophilin A results in stem cells lacking intrinsically disordered proteins necessary for HSC aging.
“Our study is the first to show that producing disordered proteins and maintaining the structural diversity of proteins in a cell plays a role in HSC aging,” Maneix emphasized.
The research team, comprising several experts in the field, explored the proteins interacting with cyclophilin A and preserving their stability, leading to the discovery of the significant role of intrinsically disordered proteins, which naturally change their three-dimensional conformation to interact with different molecules.
Cyclophilin A supports these intrinsically disordered proteins in fulfilling their functions and preventing them from aggregating, significantly impacting the stem cells’ ability to function optimally and maintain regenerative potential.
By revealing the critical role of cyclophilin A in HSC longevity, this study sheds light on the potential for future therapies targeting this enzyme for cancer treatment and understanding the aging process in HSCs.