Senescent cells — otherwise normal cells that have stopped dividing and reproducing — accumulate in various tissues and organs over time, and killing them off can extend healthy lifespan:
The scientists took advantage of the fact that one hallmark of senescent cells is that they steadily secrete a certain tumor-suppressing protein molecule called “p16Ink4a.” We’ll call it p16, and you can think of it as basically their calling card.
By rewriting a tiny portion of the mouse genetic code, Baker and van Deursen’s team developed a genetic line of mice with cells that could, under the right circumstances, produce a powerful protein called caspase when they start secreting p16. Caspase acts essentially as a self-destruct button; when it’s manufactured in a cell, that cell rapidly dies.
So what exactly are these circumstances where the p16 secreting cells start to create caspase and self-destruct? Well, only in the presence of a specific medicine the scientists could give the mice. With their highly-specific genetic tweak, the scientists had created a drug-initiated killswitch for senescent cells.
In today’s paper, Baker and van Deursen’s team reported what happened when the researchers turned on that killswitch in middle-aged mice, effectively scrubbing clean the mice of senescent cells. The medicine was injected into the genetically engineered mice’s bellies when they were 12 months old. (Keep in mind, the process isn’t perfect. Some senescent cells, including those found in the colon and liver managed to survive — possibly by avoiding the killswitch drug.)
The big takeaway is that “we saw about a 25 percent expansion of median lifespan of these mice. This held true for two different genetic strains of mice,” each engineered with the killswitch tweak, “and was irrespective of sex or the diet,” says Baker. These mice also showed delayed cancer onset, fewer cataracts, an increased drive to explore, and various other age-resistant effects in a wide range of body tissues. The body, it seems, is better off without senescent cells.
As far as the researchers could find, there was pretty much just a single downside of eliminating senescent cells: Wounds healed more slowly. That’s no big surprise, as senescent cells are known to play a role in healing and scar-tissue formation.