Restoration of aged intestinal stem cell function by exposure to a young environment
Functional decline in multiple tissues is a hallmark of aging, and is thought to be driven in part by a decline in resident stem cell function. The intestine is a prototypical example of a tissue harboring features of age-related decline in structure and function. The stem cells in the gut are responsible for maintaining the health and integrity of the intestine. However, preliminary data from Dr. Huffman’s lab show that the function of these stem cells decline with aging, and may be responsible for the overall decline of the gut.
Using an innovative surgical approach, known as parabiosis (where two animals are surgically attached in order to share their blood supply), and coupling it with a specialized assay, Dr. Huffman’s group found that exposing old mice to young blood rejuvenated these stem cells, while exposing young mice to old blood impaired function . This suggests that at least some features of gut aging can be modulated by circulating factors outside of the cell.
Thus, Dr. Huffman and his group hypothesize that key features of intestinal aging are driven in part by adverse effects of old blood, and that they are reversible. Using parabiosis and other methods, their first goal is to determine what cells lead to intestinal decline, but are affected by young blood in a way that rejuvenates old intestinal stem cell function, and whether any genetic changes in distinct types of cells might be informative to this effect. Their second goal is to determine whether this results in meaningful intestinal improvements, in vivo.