The fast-aging mouse on the left shows fur regrowth as a result of peptide treatment. The mouse on the right was untreated.
Image credit: Peter L.J. de Keizer
The research describes how the peptide stops levels of a protein called FOXO4 from increasing in senescent cells, which are cells that lose the ability to replicate and destroy themselves, but which remain metabolically active.
Senescent cells accumulate with age, and studies have shown that they can contribute to the aging process by causing damage to neighboring cells and impairing tissue function.
Previous research has shown that in senescent cells, levels of FOXO4 rise to prevent another protein called p53 from prompting the cells' self-destruction.
By blocking FOXO4 with the peptide, the research team has been able to restore programmed cell death, or apoptosis, in senescent cells.
"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.
"FOXO4 is barely expressed in non-senescent cells, so that makes the peptide interesting, as the FOXO4-p53 interaction is especially relevant to those cells, but not normal cells."
On administering the peptide to fast-aging mice in regular doses, the researchers were able to reverse age-related conditions, such as fur loss and poor kidney health.
The findings were recently published in the journal Cell.
Mice demonstrated fur regrowth within 10 days of treatment
For their study, the researchers tested the peptide on older mice that had aged naturally and mice that had been genetically modified to age rapidly.
Both groups of mice developed characteristics and health problems commonly associated with aging, such as loss of fur, a decline in kidney health, and frailty.
Some of the rodents in each group were given infusions of the peptide three times a week for 10 months, while the remaining mice were monitored as controls.
Both the fast-aging and naturally aged mice saw improvements with peptide treatment, with no apparent side effects.
Within 10 days, the fast-aging mice began to experience fur regrowth. After 3 weeks, the naturally aged mice began to see improvements in fitness, compared with mice that did not receive the peptide.
Additionally, both the fast-aging and naturally aged mice started to demonstrate improvements in kidney function from 1 month after peptide treatment.
The team notes that the effects of peptide treatment were was so strong in fast-aging mice that doses needed to be reduced over the study period.
The future of senescent cell therapy
The researchers say that their findings support previous research showing that targeting senescent cells can help to reverse aging and increase lifespan, though much more research is warranted.
"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," says de Keizer.
He and his colleagues now plan to conduct a clinical trial to assess the safety of the peptide in humans.