Library / Peptides / Longevity & Anti-Aging / FOXO4-DRI
No human data · Grade D

FOXO4-DRI

FOXO4-D-Retro-Inverso Peptide
Evidence
No Human Data
Route
Intravenous or Subcutaneous injection (in animal models)
Frequency
Not established
Category
Longevity & Anti-Aging
TL;DR
FOXO4-DRI is a D-retro-inverso peptide designed to disrupt the interaction between FOXO4 and p53 in senescent cells. Developed by Peter de Keizer's lab at Erasmus University Medical Center, it was shown to selectively induce apoptosis in senescent cells in aged mice, restoring fur density, renal function, and fitness.
Part 01 · How it works

Mechanism.

FOXO4-DRI is a D-retro-inverso peptide designed to disrupt the interaction between FOXO4 and p53 in senescent cells. Developed by Peter de Keizer's lab at Erasmus University Medical Center, it was shown to selectively induce apoptosis in senescent cells in aged mice, restoring fur density, renal function, and fitness. It is one of the first targeted senolytic peptides and has generated significant interest in the aging research field.

Remember FOXO4 as the security guard keeping the demolition expert (p53) locked up? FOXO4-DRI is a decoy that lures the security guard away from the door, freeing the demolition expert to finally tear down the damaged buildings (senescent cells) that have been causing problems.

Mechanism · technical
FOXO4-DRI is a modified version of a FOXO4 fragment that competes with endogenous FOXO4 for binding to p53 in senescent cells. By disrupting the FOXO4-p53 complex within PML nuclear bodies, it releases p53 to activate the mitochondrial (intrinsic) apoptosis pathway, selectively triggering death of senescent cells. The D-retro-inverso modification (using D-amino acids in reversed sequence) makes it resistant to proteolytic degradation while maintaining binding capability. Non-senescent cells are unaffected because they lack the FOXO4-p53 dependency.
Part 02 · Dosing & administration

How it's taken.

Values below describe how FOXO4-DRI has been administered in published trials and labeling. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.

Standard dose
Not established for humans
Intravenous or Subcutaneous injection (in animal models) · Not established
Duration
Not established

D-retro-inverso version of FOXO4 peptide for protease resistance. Preclinical only. Extremely expensive to synthesize. No human safety or dosing data.

Need help with reconstitution?

Use the free peptide calculator for dilution, unit conversion, and injection volume.

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Part 03 · Safety

Side effects, rare serious events, who shouldn't.

Reported side effects
No human safety data. In mouse studies, transient effects were observed including mild liver enzyme elevations that resolved. Theoretical risks include impaired wound healing (senescent cells play roles in tissue repair), immune suppression, and potential interference with tumor suppression mechanisms that rely on cellular senescence.
Absolute · do not use
×
Pregnancy or breastfeeding
×
Children under 18
×
Known hypersensitivity to FOXO4-DRI or any component
×
Active wound healing or recent surgery
×
Severe thrombocytopenia
Interactions
Chemotherapy agents
May interact with cancer therapy mechanisms involving cellular senescence pathways
Moderate
Immunosuppressants
Senescent cell clearance requires immune system engagement; immunosuppression may reduce efficacy
Moderate
Anticoagulants
Apoptosis of senescent cells may transiently affect inflammation and coagulation markers
Moderate
Labs to monitor
CBC with Differential
Baseline and monthly
Monitor for hematologic changes from senolytic effects
CMP (Comprehensive Metabolic Panel)
Baseline and monthly
Liver and kidney function with cell clearance
CRP / ESR
Baseline and weekly during use
Inflammatory response to senescent cell clearance
LDH
Baseline and weekly during use
Marker of cellular turnover/damage
Part 04 · Research log

Every study we cite.

Each study with its published finding and a plain-language note on limitations or funding.

01
2017
0
Targeted apoptosis of senescent cells restores tissue homeostasis
FOXO4-DRI selectively killed senescent cells, restoring fitness, fur density, and renal function in aged mice
Preclinical only; no human trials conducted
PMID 28340339 ↗
Part 05 · Cost & access

Where you can get it.

Regulatory status
Not FDA-approved. Not in clinical trials as of early 2026. Available only as a research peptide from specialty suppliers. Not a controlled substance but not approved for human use.
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Part 06 · Your appointment

Questions to bring.

01
Has FOXO4-DRI been tested in any human trials, and if not, what is the timeline?
02
How does FOXO4-DRI compare to other senolytic approaches like dasatinib + quercetin?
03
What are the risks of eliminating senescent cells — could it impair wound healing or tumor suppression?
04
Is the FOXO4-DRI available for purchase actually the same compound used in the research?