Loss of protein quality is a driving force of aging. Misfolded proteins accumulate over time and represent a vulnerability for long-lived cells, such as blood stem cells. How these cells avert the effects of aging and maintain a high regenerative potential is poorly understood. We investigated the expression and function of the most highly expressed chaperone in these cells and found a strong repression with age. We identified the target proteins of the chaperone and are currently studying how aging diminishes their folding and expression. Also, the mechanism by which chaperone expression declines with age is currently unknown.

Figure 3: The most highly expressed chaperone in hematopoietic stem cells (HSCs) declines with age (red: chaperone, blue: nucleus, scale bar = 5 μm).