Regular infusions of a peptide that can selectively seek out and destroy broken-down cells that hamper proper tissue renewal, called senescent cells, showed evidence of improving healthspan in naturally-aged mice and mice genetically engineered to rapidly age. The proof-of-concept study, published March 23 in Cell, found that an anti-senescent cell therapy could reverse age-related loss of fur, poor kidney function, and frailty. It is currently being tested whether the approach also extends lifespan, and human safety studies are being planned.
The peptide took over four years of trial and error to develop and builds on nearly a decade of research investigating vulnerabilities in senescent cells as a therapeutic option to combat some aspects of aging. It works by blocking the ability of a protein implicated in senescence, FOXO4, to tell another protein, p53, not to cause the cell to self-destruct. By interfering with the FOXO4-p53 crosstalk, the peptide causes senescent cells to go through apoptosis or cell suicide.
“Only in senescent cells does this peptide cause cell death,” says senior author Peter de Keizer, a researcher of aging at Erasmus University Medical Center in the Netherlands. “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.”
“This wave of research on how we can fight aging is complementary, and not in competition,” says de Keizer. “The common thread I see for the future of anti-aging research is that there are three fronts in which we can improve: The prevention of cellular damage and senescence, safe therapeutic removal of senescent cells, to stimulate stem cells — no matter the strategy — to improve tissue regeneration once senescence is removed.”