Disposing of cellular “litter”—cells that no longer divide—may be the key to human life-extension, according to a new study published Wednesday in Nature. The study provides promising direction for research on longevity and a target for new drug development.
Researchers at the Mayo Clinic have found that senescent cells, as they’re called (from the Latin word that means “to grow old”), accumulate and are a cause of aging and the development of age-related diseases like cancer. In their study on mice, the researchers found clearing senescent cells increased life span by as much as 35 percent.
“What we found is as we are aging, we accumulate more and more of those dead cells,” says Jan van Deursen, chair of biochemistry and molecular biology at the Mayo Clinic and co-author on the study. “But they are not innocent bystanders; they secrete a number of proteins that have a negative impact on the surrounding cells and deregulate those cells.” He added this cellular garbage causes organs to function less optimally.
For the study, the researchers genetically modified normal mice so they would respond to a compound called AP20187, which was originally developed as an anti-cancer drug. “Cancer cells are stressed cells that have survived and senescent cells seem to do the same thing,” says van Deursen. In other words, in the mice, AP20187 would eliminate their senescent cells.
In addition to helping these modified mice live 17 to 35 percent longer than the normal mice, the drug also delayed the formation of tumors and reduced age-related deterioration of several organs. The mice also looked healthier and had lower levels of inflammation in fat, muscle and kidney tissue.
The process didn’t negatively affect the functions of the mice, and according to van Deursen it isn’t even necessary to remove all of the cellular litter for there to be some therapeutic benefits. By his estimates, only about 50 to 78 percent of these cells actually need to be eliminated for it to be effective.
Unfortunately, AP20187 would only be effective in humans if it were taken in such large doses that would make it intolerable and toxic, says van Deursen. However, the new findings are significant in the research field of life-extension—there are a number of pharmaceutical companies currently working on developing drugs that harness this concept of taking out cellular trash.