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Longevity

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Senolytic peptide (preclinical)

FOXO4-DRI

Also known as: FOXO4-D-Retro-Inverso, Senolytic peptide (Baar 2017), FOXO4 D-Retro-Inverso peptide

Senolytic peptide designed to selectively kill aged cells. Mouse data only — no published human trials.

Reviewed 2026-05-05

What it does

FOXO4-DRI is a synthetic peptide designed to selectively kill senescent cells — the "zombie cells" that accumulate with age and contribute to age-related decline. The 2017 mouse data showed striking results: aged mice given the peptide IV had reduced frailty, restored fur density, improved kidney function, and better endurance. The longevity community uses it as a senolytic peptide to target aged cells. There are no published human trials.

Used for

Dose

Starting
5 mcg · every 2–3 days for 3 doses, then cycled
Common
28 mcg · every 2–3 days for 3 doses, then cycled
Upper
50 mcg · every 2–3 days for 3 doses, then cycled
When
MorningSingle-source mouse paper, no human chronopharmacology. Morning timing for the day-on / day-off senolytic cycling typical of this class lets the user track subjective effects.
Site
intravenous (mouse extrapolation)

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⚠ Caution

  • Any active malignancy (selectively triggering apoptosis is not benign in patients with mixed-population tumors and pre-malignant lesions)
  • Pregnancy and breastfeeding (no safety data)
  • Pediatric and adolescent use (inappropriate for any preclinical-only compound outside trials)
  • Active or recent chemotherapy / radiation (combined apoptotic stress is uncharacterized)
  • Known hypersensitivity
  • Use without informed-consent acknowledgment that this is preclinical-only

Your stack

Track this peptide in your protocol — dose, schedule, vials on hand, refill projection. Stays in your browser; no account needed.

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Use this peptide

Featured in protocols
  • Longevity — Phase 3 — Senolytic + pineal layer (cyclical, optional)
Reconstitution & storage

Vendor preparations are typically lyophilized powder reconstituted with sterile saline or BAC water for IV / SubQ use. Injection volumes for 'senolytic-protocol' doses can be substantial. There is no validated commercial-grade formulation.

Storage. Vendor-dependent. Lyophilized powder typically refrigerated; reconstituted within 7–14 days due to limited stability data.

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Monitoring & questions

Reported side effects
  • Unknown in humans — no published Phase 1 safety data
  • Anecdotal community / clinic reports: flu-like symptoms during the first 24–48 hours after dosing (consistent with a cytokine-release-like response that would be expected from large-scale senescent-cell apoptosis); these reports are uncontrolled
  • Theoretical: off-target apoptotic induction in non-senescent cells with high FOXO4 dependency
  • Theoretical: any senolytic carries hypothetical risk if the senescent state is performing useful biology (e.g., wound-healing senescence, tumor surveillance)

Reference

How it works

Disrupts FOXO4-p53 binding in senescent cells, releasing p53 to trigger apoptosis selectively in cells that have entered senescence (senescent cells over-express FOXO4 and are 'addicted' to FOXO4-p53 interaction for survival). Healthy cells should be unaffected because the FOXO4-p53 binding is not critical for their survival. The retro-inverso D-amino-acid design is intended to extend half-life and resist proteolytic degradation, allowing the peptide to reach intracellular targets after IV administration.

Juno's take

The mouse data is real and striking, but it's a single mouse study from 2017 and no human RCTs have been published since. Vendor and longevity-clinic use is extrapolation from rodents to humans — a leap the underlying mechanism doesn't obviously support at human doses or in human physiology. The "reset cellular age" marketing this peptide gets is exactly the kind of claim that runs ahead of the evidence. Treat this as preclinical-only until a human trial publishes.

EvidenceTier 4 — Anecdotal

Tiers are per indication. The same molecule can be Tier 1 for one use and Tier 4 for another — the tier reflects published literature, not community framing.

Senescent-cell clearance / 'cellular reprogramming' in aged mice

Tier 4high confidence

Single landmark study (Baar 2017, Cell) demonstrating preferential senescent-cell killing and frailty-marker improvement in aged mice. Effect size was striking. There is no replication in independent human or non-human primate work, and no completed published human trial.

Baar MP et al. 2017

Anti-aging / longevity in humans

Tier 4high confidence

No human RCT. No published Phase 1 safety data. Community framing as a 'reset for cellular age' has zero translational evidence. Mechanism-as-evidence reasoning, with the additional caveat that systemic apoptotic-induction peptides have very real safety questions in untrialed populations.

No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.

Citations (1)
  1. [1]
    Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging
    Baar MP, Brandt RMC, Putavet DA, et al. (de Keizer PLJ, group) · Cell · 2017 · PMID 28340339
    The single landmark mouse study underlying all FOXO4-DRI claims. Only published preclinical anchor.
    View source