FOXO4-DRI

Research ChemicalPreliminary Research

Also known as: FOXO4-D-Retro-Inverso · Senolytic Peptide · Proxofim

A senolytic peptide that selectively induces apoptosis in senescent cells by disrupting the FOXO4-p53 interaction, effectively clearing 'zombie cells' that drive aging.

Overview

FOXO4-DRI is a D-retro-inverso peptide designed to selectively eliminate senescent cells — often called 'zombie cells' — that accumulate with age and drive chronic inflammation, tissue dysfunction, and age-related disease. Senescent cells resist normal apoptosis (programmed cell death) by maintaining a survival interaction between the FOXO4 transcription factor and the p53 tumor suppressor protein. FOXO4-DRI is engineered to disrupt this specific interaction, releasing p53 from FOXO4 sequestration and allowing it to trigger apoptosis selectively in senescent cells. Healthy cells, which do not depend on the FOXO4-p53 interaction for survival, are unaffected.

In groundbreaking research published in Cell, FOXO4-DRI treatment in aged mice restored fitness, fur density, and renal function — essentially reversing aspects of aging. This represents one of the most targeted senolytic approaches available.

Mechanism of Action

A D-retro-inverso peptide that competitively disrupts the FOXO4-p53 protein-protein interaction in senescent cells. When FOXO4 is displaced from p53, p53 is released to the mitochondria where it triggers intrinsic apoptosis specifically in senescent cells. The D-amino acid retro-inverso design provides protease resistance and enhanced cellular penetration.

Key Benefits

Selective elimination of senescent cells
Reduced chronic inflammation (inflammaging)
Potential reversal of age-related tissue dysfunction
Improved organ function in aged models
Targeted mechanism spares healthy cells
One of the most specific senolytic approaches

Potential Side Effects

Flu-like symptoms during senescent cell clearance
Temporary fatigue
Injection site reactions
Limited human safety data

Common Stacks

This peptide is commonly combined with the following compounds for synergistic effects:

RapamycinMetforminNAD+ / NMNSS-31

Known Interactions

The following interactions have been documented for FOXO4-DRI. Always consult a healthcare professional before combining compounds.

Synergistic (1)

RapamycinSynergistic

FOXO4-DRI is a senolytic (clears senescent cells) while rapamycin inhibits mTOR to slow cellular aging. Complementary: clear damaged cells + slow aging of remaining cells.

View all compound interactions

Scientific References

Quick Reference

Typical Dose

5mg

Frequency

1x daily

Route

Subcutaneous injection

Half-Life

~12-24 hours (D-amino acids resist proteolysis)

Cycle Length

3 days on, followed by 2-6 months recovery

FDA Status

Research compound — not FDA approved. Preclinical data published in Cell (2017).

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This information is for educational purposes only. Consult a qualified healthcare professional before using any peptide. Dosing information reflects commonly reported protocols and may not be appropriate for everyone.

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