Researchers here use the properties of a subset of natural killer T cells of the immune system in order to provoke these cells into greater activity without rousing the rest of the immune system into action. The outcome is that the activated natural killer T cells then destroy more senescent cells than would otherwise have been the case. Destroying senescent cells by any means leads to a dose-dependent degree of rejuvenation in older individuals, and that result is achieved here. This is an intriguing approach to the challenge of clearing senescent cells, and it will be interesting to watch its further development.
In a healthy state, these immune cells - known as invariant Natural Killer T (iNKT) cells - function as a surveillance system, eliminating cells the body senses as foreign, including senescent cells, which have irreparable DNA damage. But the iNKT cells become less active with age and other factors like obesity that contribute to chronic disease. The iNKT cells have two attributes that make them an especially appealing drug target. First, they all have the same receptor, which does not appear on any other cell in the body, so they can be primed without also activating other types of immune cells. Second, they operate within a natural negative feedback loop that returns them to a dormant state after a period of activity.
Researchers found they could remove senescent cells by using lipid antigens to activate iNKT cells. When they treated mice with diet-induced obesity, their blood glucose levels improved, while mice with lung fibrosis had fewer damaged cells, and they also lived longer. The results presented for iNKT cells in a mouse model of lung fibrosis offer hope for a potentially fatal disease that often leads to lung transplants. "I think this is a potential immune therapy for senescence and fibrosis. It's a fairly well tolerated therapy, and we just have to get around dosing and trials."