library.onepin.app/foxo4-dri Peptide Education Library

Education only, not medical advice◆ 21+◆ Every dose is an example to finalize with a licensed provider

OnePin Peptide Library · Longevity

Longevity Synthetic D-retro-inverso peptide Not FDA-approved · investigational

FOXO4-DRI

FOXO4-D-Retro-Inverso · FOXO4-DRI Senolytic

Synthetic D-retro-inverso peptideSenolytic agentFOXO4-p53 interaction disruptorSenescent cell apoptosis inducer

FOXO4-DRI is a synthetic D-retro-inverso peptide that disrupts the interaction between FOXO4 transcription factor and p53 in senescent cells. Senescent cells are damaged cells that have stopped dividing but resist apoptosis, accumulating with age and secreting inflammatory factors (SASP - senescence-associated secretory phenotype) that damage surrounding tissue. FOXO4-DRI selectively triggers apoptosis in senescent cells by preventing FOXO4 from sequestering p53 in the nucleus, allowing p53 to relocate to mitochondria and initiate cell death. This senolytic (senescent cell clearing) mechanism was published in Cell (2017) by Peter de Keizer's group.

Quick Start

Route

SubQ injection

Start low

Varies; protocols use mg/kg calculations

Frequency

Intermittent dosing protocols

Timing

No data

Run BEFORE repair peptides (senolytics clear senescent cells first, then rebuild). Any time of day. 3 doses EOD then months off.

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Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.

Tiered Protocols · lowest first

Quick Start

Conservative start

Varies; protocols use mg/kg calculations · SubQ injection · Intermittent dosing protocols

Lowest starting point. Hold about a week to assess tolerance before stepping up.

Varies; protocols use mg/kg calculations

Intermittent dosing protocols

Expert

Senescent Apoptosis

3 mg · SubQ · Every other day

animal study · Baar et al. 2017 (Cell)

3 mg

Every other day

Reconstitution CalculatorU-100

Vial strength

BAC water

Target dose

050100u

Draw to

— units

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How it works

In senescent cells, FOXO4 binds p53 and sequesters it in the nucleus via PML (promyelocytic leukemia) nuclear bodies, preventing p53 from triggering apoptosis at the mitochondria. FOXO4-DRI is a modified peptide that competitively disrupts this FOXO4-p53 interaction. Once freed, p53 translocates to the mitochondrial outer membrane, activates Bax/Bak pore formation, releases cytochrome c, and triggers intrinsic apoptosis. Critically, this mechanism is selective for senescent cells because healthy cells do not rely on FOXO4-p53 nuclear sequestration for survival. The D-retro-inverso modification (D-amino acids in reversed sequence) provides resistance to proteolytic degradation while maintaining biological activity.

What to expect

Early

Days 1–7

Days 1-7: No perceptible changes.

Mid

Weeks 2–4

Weeks 2-8: Senescent cell clearance occurs. SASP reduction begins.

Later

Weeks 4–12

Months: Tissue renewal. Best assessed through biomarkers (p16, SASP markers).

Evidence

HumanNo published trials

AnimalPresent

In-vitroPresent

2017Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging · Baar MP, Brandt RMC, Putavet DA, et al, Cell ↗peer reviewed

2021Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes · Lim H, Park H, Kim HP, Frontiers in Bioengineering and Biotechnology ↗peer reviewed

The honest take

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Selective senolytic

Supported

Published in Cell (2017). Selectivity for senescent cells confirmed in vitro and animal models. One of the few purpose-designed senolytic peptides.

Anti-aging

Senescent cell accumulation is a recognized hallmark of aging. Clearance improves tissue function in animal models. Human longevity data not available.

Interactions & stacking

What's safe to combine, and what belongs in a separate pin.

Safe & synergistic

BPC-157FOXO4-DRI clears senescent cells, BPC repairs tissue

HumaninFOXO4-DRI clears, Humanin protects remaining cells

SS-31FOXO4-DRI clears senescent cells, SS-31 optimizes mitochondria in remaining healthy cells. Clear the damaged + boost the healthy.

Keep separate

CJC-1295 with DACDAC maleimide reactivity.

Side effects & safety

Commonly reported

Limited data
Injection site irritation

Less common & notes

Theoretical concerns about off-target apoptosis in non-senescent cells.
The D-retro-inverso modification provides selectivity but human safety data is absent.
Use with caution.
Newest compound in the database with least safety data.

Pharmacokinetics

Illustrative plasma concentration · 24 h

Half-life

Peak · Tmax

Elimination

30h

Activity

24-72 hours (senolytic apoptosis cascade continues after peptide clearance)

Storage. Limited published stability data. Conservative 28-day estimate. BAC water 2-8C.

Regulatory status

Not FDA-approved. Research peptide only. Newest and least established compound in the database.

Put it to work

Calculate, log & track

Open FOXO4-DRI straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.

Open FOXO4-DRI in the app →

Go deeper

The guide & community

The complete FOXO4-DRI walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.

Join the community ↗

Open in app Community