LONGECITY

Researchers here report on the importance of molecular chaperones, and cyclophilin A in particular, to the function of hematopoietic stem cells. These cells generate red blood cells and immune cells, and thus age-related changes in hematopoietic function have important consequences for health. The immune system runs awry with age, and altered hematopoiesis is one of the contributing factors. If, as researchers here suggest, upregulation of cyclophilin A can improve hematopoietic stem cell function, then using this as a basis for therapy may produce health benefits in older individuals.

Hematopoietic stem cells (HSCs) are remarkably long-lived. HSCs typically remain dormant within the bone marrow, yet they possess the ability to activate and replenish blood cells continuously, maintaining a relatively youthful profile throughout the life of an organism. A driving force of cellular aging is the accumulation of proteins that have reached the end of their useful life. With age, proteins tend to misfold, aggregate, and accumulate inside the cell, which leads to toxic stress that can disrupt cell function. Cells that frequently engage in cell division, like progenitor cells, can dispose of protein aggregates through dilution. On the other hand, long-lived HSCs, which do not divide often, face the problem of the accumulation of misfolded proteins and subsequent toxic stress. Nevertheless, HSCs remain impervious to aging. How do they do it?

Previous studies have shown that mammalian cells express hundreds of molecular chaperones, proteins that preserve or change the three-dimensional conformation of existing proteins. Cyclophilins, one of the most abundant chaperones, have been implicated in the aging process. However, how they affect cellular proteins has not previously been studied. Working with mice, the researchers first characterized the protein content of HSCs and discovered that cyclophilin A is a prevalent chaperone. Further experiments showed that the expression of cyclophilin A was significantly decreased in aged HSCs, and genetically eliminating cyclophilin A accelerated natural aging in the stem cell compartment. In contrast, reintroducing cyclophilin A into aged HSCs enhanced their function. Together, these findings support cyclophilin A as a key factor in the longevity of HSCs.

Link: https://blogs.bcm.ed...ved-stem-cells/