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Longevity & mitochondrial

FOXO4-DRI

Also called FOXO4 D-retro-inverso peptide

FOXO4-DRI is a lab-made peptide designed to kill 'senescent' cells, old damaged cells that stop dividing but linger and cause inflammation. A 2017 mouse study made headlines when it restored fur, fitness and kidney function in old mice. It has never been tested in a published human trial.

Preclinical onlyStudied in cells or animals only. Effects in people are unknown.

All printable flashcards

Illustrative chain. The exact sequence has not been published in a source we could verify.

Overview

FOXO4-DRI is a lab-made peptide designed to kill 'senescent' cells, old damaged cells that stop dividing but linger and cause inflammation. A 2017 mouse study made headlines when it restored fur, fitness and kidney function in old mice. It has never been tested in a published human trial.

How it works

Proposed from cell and animal studies. In senescent cells, the protein FOXO4 binds p53 in the nucleus and helps keep those cells alive instead of letting them self-destruct. FOXO4-DRI is designed to block that FOXO4-p53 contact; p53 is then pushed out of the nucleus and the senescent cell undergoes apoptosis (programmed cell death), while normal cells appear largely spared 1. Later mouse and cell studies reported the same pathway, with activation of BAX and cleaved caspase-3 3. Not established in humans.

What research shows

  • Baar et al. 2017, Cell (mouse and cell study): FOXO4-DRI selectively triggered death of senescent cells, countered doxorubicin chemotherapy toxicity, and restored fitness, fur density and kidney function in fast-aging and naturally aged mice 1.
  • Zhang et al. 2020, Aging (cell and aged-mouse study): raised blood testosterone and lowered senescence markers in aged male mice; authors note no direct proof that senescent Leydig cells were removed in vivo 2.
  • Huang et al. 2021, Front Bioeng Biotechnol (lab study): removed many senescent cells from expanded human cartilage cells but did not improve cartilage-forming ability in standard culture 4.
  • Hu et al. 2026, Front Bioeng Biotechnol (aged and prematurely aged mice, endothelial cells): reduced aortic senescence markers and improved arterial stiffness; authors say the work is still preclinical 3.
  • No published human trials were found.

Doses studied in people

No published human dosing data exist; doses circulating online are extrapolated from mouse studies (typically given by injection into the abdomen).

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Weekly protocol

How the schedule looks week by week. Each chart says where it comes from: a prescribing label, a clinical trial, or a protocol commonly reported online.

PeptideDosages.com daily protocol

Commonly reported, not studied

One week

D1D2D3D4D5D6D7

Once daily · Subcutaneous injection

Syringe units (U-100)

Dose by week

250 mcgwk 1–4
375 mcgwk 5–8
500 mcgwk 9–16

Supplies for one course (estimate)

Counts only. This site does not sell or link to supplies.

Course
8–16 weeks
Note
No human safety or efficacy data exist.
Source
PeptideDosages.com: FOXO4-DRI (10 mg vial) dosage protocol

Short 'hit-and-run' course

Commonly reported, not studied

One week

D1D2D3D4D5D6D7

Every other day · Subcutaneous injection

Syringe units (U-100)

Dose by week

3–25 mg per injection (highly variable)wk 1–2

Supplies for one course (estimate)

Counts only. This site does not sell or link to supplies.

Course
3–6 doses per course, repeated 1–3 times a year
Note
Loosely modelled on the mouse study (5 mg/kg IV three times a week). No established human dose.
Source
Peptide Protocol Wiki: FOXO4-DRI dosing protocols

Reference only, not a recommendation. Charts marked "commonly reported" describe what public sources say people use. They have not been tested in trials, and their safety and effect are unknown. Label and trial schedules were set for specific patients under medical supervision. Use the calculator only to understand the arithmetic.

Vial math

Many research vials hold 5 or 10 mg of powder. This table shows how much ends up in each mark on a U-100 insulin syringe for common amounts of added liquid. It is arithmetic only, not a dose.

VialLiquid addedConcentrationPer unit (0.01 mL)
5 mg1 mL5 mg/mL50 mcgOpen in calculator
5 mg2 mL2.5 mg/mL25 mcgOpen in calculator
5 mg3 mL1.67 mg/mL16.7 mcgOpen in calculator
10 mg1 mL10 mg/mL100 mcgOpen in calculator
10 mg2 mL5 mg/mL50 mcgOpen in calculator
10 mg3 mL3.33 mg/mL33.3 mcgOpen in calculator

More sizes: all vial sizes · How this works: Syringes and units · Reconstitution guide.

Safety

  • No human safety data; short- and long-term risks are unknown.
  • In mice it was reported as well tolerated over short courses 1, but mouse tolerance does not predict human safety.
  • p53 is a key tumor-suppressor protein; the long-term effect of altering its location in cells has not been studied in people.
  • Unregulated 'research' products may vary in purity and identity.

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

History

Developed by Peter de Keizer and colleagues at Erasmus University Medical Center in the Netherlands, with collaborators including Judith Campisi; published in Cell in 2017 1. A start-up, Cleara Biotech, was later formed to develop therapies based on the FOXO4-p53 concept, and has remained preclinical according to a 2026 commentary 5. Independent groups have since tested it in aged-mouse Leydig cells (2020), human cartilage cells (2021) and blood vessels (2026) 243.

Common questions

Has FOXO4-DRI been tested in humans?

No published human trials exist; all evidence comes from mice and cells in the lab 13.

What did the famous 2017 study show?

In old and fast-aging mice, FOXO4-DRI cleared senescent cells and improved fur, fitness and kidney function 1.

Is FOXO4-DRI approved?

No. It is an experimental compound with no approval anywhere and is not on FDA's compounding lists 67.

Is FOXO4-DRI banned in sport?

It is not named on the 2026 WADA list, but unapproved substances are generally covered by the S0 ban 8.

Related compounds

Sources

  1. Baar MP, Brandt RMC, Putavet DA, et al. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell 2017;169(1):132-147.e16. doi:10.1016/j.cell.2017.02.031 Journal
  2. Zhang C, Xie Y, Chen H, et al. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging (Albany NY) 2020;12(2):1272-1284. doi:10.18632/aging.102682 Journal
  3. Hu Z, Li F, Hu C, et al. FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway. Front Bioeng Biotechnol 2026;13:1729166. doi:10.3389/fbioe.2025.1729166 Journal
  4. Huang Y, He Y, Makarcyzk MJ, Lin H. Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Front Bioeng Biotechnol 2021;9. doi:10.3389/fbioe.2021.677576 Journal
  5. Fight Aging! People Are Still Working on the Senolytic Peptide FOXO4-DRI (Feb 2026; commentary, used only for company status) Commentary
  6. FDA: Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026) Regulatory
  7. FDA: Bulk Drug Substances Nominated for Use in Compounding Under Section 503A (category lists) Regulatory
  8. WADA 2026 Prohibited List (official English text, Dutch Treaty Series Trb. 2026, 25) Regulatory

Last reviewed 2026-10-26 · How we research · Found an error? See our corrections policy.