Flushing out old cells from the body has been found to rejuvenate aging mice, giving hope to the possibility that in the future a drug could, in part, reverse aging.
The study hinges on what happens to aging cells in the body. As we get older, our cells start to build up damage in our DNA, which eventually reaches a point in which it cannot be repaired. Once it gets to this milestone, one of three things happen: The cell either dies, it turns cancerous, or it enters a state known as senescence. In this state, the cells are in effect dormant, as they have stopped dividing but still persist.
It has long been thought that these senescent cells were fairly harmless, as they continued to hang around in the body and play a part in wound healing.
However, research has revealed that the senescent cells are in fact leaching a whole cocktail of chemicals and molecules that may be disrupting the healthy cells that surround them, potentially causing inflammation and even aging.
After four years of trial and error, researchers from the Erasmus University Medical Center in the Netherlands have managed to find a particular peptide molecule that seems to selectively kill these senescent cells, while leaving healthy tissue alone. They found that it restored function to some of the organs in aging mice, patches of missing fur grew back (as their kidneys started to function again), and older mice could run twice the distance of their non-treated counterparts.
It works by targeting a particular protein, FOXO4, which in normal senescence is thought to stop the cell from dying. They found that FOXO4 instructed another protein, p53, to prevent the cell from self-destructing. By preventing the first protein from talking to the second, they found that the cell would in effect commit suicide.
“Only in senescent cells does this [protein] cause cell death,” explains Peter de Keizer, senior author of the paper published in Cell, in a statement. “We treated mice for over 10 months, giving them infusions of the peptide three times a week, and we didn't see any obvious side effects. FOXO4 is barely expressed in non-senescent cells, so that makes the peptide interesting as the FOXO4-p53 interaction is especially relevant to senescent cells, but not normal cells.”
After the successful trials on mice, their plan is to move to human subjects. The study is being viewed with restrained interest from other researchers. The results are clearly fascinating, but it will be a different matter to see how, or if, they translate to people.