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Biological Chemistry

Clearing senescent cells revitalizes aging mice

A designed therapeutic peptide sends senescent cells on the path to death, restoring fur thickness and kidney function, making mice more active

by Sarah Everts
March 27, 2017 | A version of this story appeared in Volume 95, Issue 13

Credit: Peter L. J. de Keizer
Elderly mice treated with antiaging peptides have thicker fur (left) than their untreated cohorts (right).
Photo of two mice.
Credit: Peter L. J. de Keizer
Elderly mice treated with antiaging peptides have thicker fur (left) than their untreated cohorts (right).

As we age, our cells increasingly become senescent: Instead of dying, these decrepit cells stop dividing and begin secreting a cocktail of molecules that can cause problems for other cells. Scientists have long been searching for chemical treatments that can clear away the problematic cells. Now, a team of researchers led by Peter L. J. de Keizer at Erasmus University Medical Center Rotterdam are reporting that a cell-penetrating peptide they prepared can make senescent cells in mice suicidal, allowing the animals to remove them naturally. The peptide is a shortened form of a protein called FOXO4. In senescent cells, FOXO4 binds another protein, called p53. This interaction prevents cell death. When delivered to mice, the team found that the peptide disrupts the normal FOXO4-p53 interaction and the cells are directed to die (Cell 2017, DOI: 10.1016/j.cell.2017.02.031). The researchers tested the treatment on elderly mice and found that these animals had thicker fur, healthier kidneys, and were more active compared with controls. Given that young, healthy cells don’t produce much FOXO4, de Keizer believes the peptide is unlikely to have many side effects on normal cells. The team hopes to test the peptide soon in humans. “With life expectancy projected to increase in the foreseeable future, it is important to develop strategies to extend and restore health span,” the researchers note.


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