Senolytic peptide · Also known as FOXO4-D-Retro-Inverso, Proxofim
A D-retro-inverso peptide designed to selectively eliminate senescent ("zombie") cells by disrupting the interaction between FOXO4 and p53 proteins. It forces senescent cells into apoptosis while leaving healthy cells unharmed.
FOXO4-DRI was developed by researchers at Erasmus University Medical Center in the Netherlands and published in Cell in 2017. The peptide demonstrated the ability to reverse aspects of aging in naturally aged mice, including restoring fur density and kidney function. Cleara Biotech was formed to commercialize this research, though the compound remains in preclinical development.
Senescent cells accumulate with age and secrete inflammatory molecules that damage surrounding tissue. These cells survive because FOXO4 protein binds to p53 in the nucleus, preventing p53 from triggering apoptosis (programmed cell death). Essentially, FOXO4 acts as a bodyguard keeping senescent cells alive.
FOXO4-DRI is engineered to compete with endogenous FOXO4 for p53 binding. When it disrupts this interaction, p53 is released from the nucleus and translocates to the mitochondria, where it triggers the intrinsic apoptosis pathway. Because healthy cells have low levels of both FOXO4 and nuclear p53, the peptide is selective for senescent cells. In animal studies, FOXO4-DRI showed an 11.7-fold selectivity for senescent cells over normal cells.
250 mcg/day subcutaneous
Weeks 1-4250-500 mcg/day subcutaneous
8-16 week cyclesMost side effects tend to improve as your body adjusts.