FOXO4-DRI

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Quick Facts

Full Name: FOXO4 D-Retro-Inverso Peptide
Aliases: FOXO4-DRI, FOX04-DRI, Proxofim
Category: Senolytic / Longevity / Cellular Health
Type: D-retro-inverso (DRI) peptide — mirror image of native sequence for protease resistance
Molecular Weight: ~3.5 kDa
Administration: Subcutaneous / Intraperitoneal (research)
Typical Dose: 1–3 mg/kg SubQ
Frequency: 3 injections/week or pulsed protocols
Status: Research Only (preclinical / early human experimentation)
WADA Status: Not listed

What It Does

FOXO4-DRI is a senolytic peptide that selectively eliminates senescent cells — damaged, dysfunctional cells that accumulate with age and drive inflammation (the "senescence-associated secretory phenotype" or SASP). By disrupting the FOXO4-p53 interaction that keeps senescent cells alive, it triggers apoptosis specifically in these harmful cells while leaving healthy cells unaffected. Landmark mouse studies showed restoration of fitness, fur regrowth, and improved kidney function after treatment.

Mechanism of Action

FOXO4-p53 interaction disruption: Senescent cells upregulate FOXO4, which sequesters p53 in the nucleus and prevents apoptosis. FOXO4-DRI competitively inhibits this interaction → p53 released → cytoplasmic p53 → apoptosis in senescent cells
Senescent cell selectivity: Normal cells have low FOXO4 expression and are not affected — selective killing mechanism
SASP reduction: Clearing senescent cells reduces the inflammatory SASP (IL-6, TNF-α, MMP secretion) → systemic anti-inflammatory effect
D-retro-inverso design: Mirror-image amino acids + reversed sequence → complete protease resistance → superior in vivo stability vs. native peptide
Tissue rejuvenation: Removal of senescent cells allows tissue stem cell niche to recover and regenerate

Ageless Peps Products

APWS-FOXO4DRI-Vial — FOXO4-DRI 10mg Vial, wholesale only (draft status)

Dosing Protocols

Research-Informed Pulsed Protocol

Dose: 1–3 mg/kg SubQ (translate to body weight)
Frequency: 3x per week for 3 weeks (pulsed approach)
Rest period: 3–6 months before repeat cycle (allow tissue recovery)
Note: "Less is more" — pulsed low-dose may be safer than continuous high-dose
Source: The Peptides Bible, van Deursen group research (Nature 2017)

Stacks Well With

GHK-Cu – tissue regeneration after senescent cell clearance; promotes repair signaling
GDF-11 – tissue rejuvenation and systemic youthful signaling post-senolysis
Epitalon – longevity and telomere support complement
BPC-157 – tissue repair support post-senolytic cycle

Use Cases

Longevity (senescent cell burden reduction)
Healthspan Extension (delay age-related functional decline)
Tissue Rejuvenation (skin, kidney, liver, muscle)
Inflammation Reduction (SASP clearance)
Frailty reversal

Contraindications & Safety

Active malignancy — apoptotic mechanism; untested safety in cancer; avoid
Post-chemotherapy — chemotherapy-induced senescence may be protective in some contexts; caution
Autoimmune conditions — immune system changes post-senolysis; monitor
Aggressive dosing — excessive senescent cell clearance may impair wound healing (senescent cells have roles in acute healing)
Limited human safety data — extrapolated from mouse studies; use with caution
Common side effects in animal models: Transient fatigue, injection site reactions

Storage

Lyophilized: -20°C long-term; 2–8°C up to 3 months
Reconstituted: 2–8°C for 1–2 weeks; protect from light
Solvent: Sterile/bacteriostatic water

PubMed Research

Research links will be added after PubMed search

Sources

The Peptides Bible – Senolytic peptides section
Peptide Protocols Master Bible – Longevity protocols
Baar et al., Cell 2017 — landmark FOXO4-DRI mouse study

#senolytic #longevity #aging #senescence #SASP #cellular-health #rejuvenation #peptide