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Longevity

FOXO4-DRI

A senolytic peptide meant to push aging (senescent) cells into cell death, an exciting but purely preclinical anti-aging approach.

2 min read 7 sources

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Vial with white powder, a blue cap and a black TPD label for FOXO4 on a white podium, next to it a large, branched molecule model of blue and white glass spheres in a bright lab
Preclinical · not approved

Summary

At a glance

Sources checked on 26 Oct 2026

Selective for old cells
11.7 -fold

stronger effect on senescent than on normal human fibroblasts (cell culture)1

Dying old Leydig cells
27 %

versus 10 percent without FOXO4-DRI, mouse cell culture3

Cells removed
>50 %

in long-expanded human cartilage cells, little effect on fresh ones4

Human trials
0 trials

no trial with FOXO4-DRI on ClinicalTrials.gov, as of 26 Oct 20266

  • FOXO4-DRI is a senolytic: a peptide that specifically targets senescent cells, meaning old cells that no longer divide and release inflammatory substances.1
  • In these cells the protein FOXO4 holds the guardian p53 in the nucleus. FOXO4-DRI disrupts this binding, p53 is released and the old cell dies. Normal cells are largely spared.12
  • In old mice fitness, fur and kidney function came back. In further studies testosterone rose in old mice.13
  • Senolytics are not harmless: in mice removing old vessel cells worsened pulmonary hypertension.5
  • ClinicalTrials.gov lists no human trial (as of October 2026). Everything here is preclinical research, not a recommendation.6
Profile

Updated May 2026

Class
Senolytic peptide

FOXO4-p53

Use
Subcutaneous

in mg

Half-life
short
Status
Preclinical

no human data

Sizes
2 to 16 mg

3 sizes in the shop

Contents 15 sections
  1. At a glance
  2. What is FOXO4-DRI?
  3. How it works
  4. What you need
  5. Reconstitution
  6. Dosing
  7. Injection
  8. What the research shows
  9. Research status
  10. Side effects
  11. Storage
  12. Related compounds
  13. FAQ
  14. Glossary
  15. Sources

What is FOXO4-DRI?

FOXO4-DRI is a senolytic peptide, a compound that specifically attacks senescent cells, the old, no-longer-dividing cells that accumulate with age and promote inflammation. The idea: remove these "zombie cells" and so rejuvenate tissue.

Up front: exciting mechanism, but purely preclinical, no human data.

Comparison

Anti-ageing approaches in the lexicon

Where each compound acts, as stated in the TPD lexicon. Tap a card to open its entry.

Senolytic, removes old cells FOXO4-DRI p53
Tetrapeptide, telomerase Epitalon Telomerase Peptide from the mitochondria MOTS-c AMPK Peptide for the mitochondrial membrane SS-31 (Elamipretide) Mitochondria

How it works

In senescent cells the protein FOXO4 keeps the tumor suppressor p53 in the nucleus and so prevents the cell from going into programmed cell death. FOXO4-DRI specifically disrupts this FOXO4-p53 binding, p53 is freed and the senescent cell dies, while healthy cells are largely spared.

Where it acts

Where FOXO4-DRI acted in experiments

Tap a point or a card. Colour = target, grey = observed. All from cell and animal studies.

  1. Kidney

    Kidney function better again in fast-ageing and naturally aged mice1

    Observed in trials
  2. Fur and skin

    Denser fur in old mice1

    Observed in trials
  3. Testes

    Old Leydig cells died selectively, testosterone in old mice rose3

    p53
  4. Cartilage cells

    More than half of old cells removed, but cartilage formation not better (cell culture)4

    p53
  5. Lung vessels

    Pulmonary hypertension in mice worsened when old vessel cells were removed5

    Observed in trials

Known targets2

Compound PubChem CID 167312269: one described target, Binds to the TAD2 region of p53 and displaces FOXO4 (NMR structure).

Tumour suppressor p53
Gene
TP53
UniProt
P04637
ChEMBL
CHEMBL4096
Action
Binds to the TAD2 region of p53 and displaces FOXO4 (NMR structure)
Many clear glass cells, in the centre a dull, aged cell that blue molecules enter and that breaks up into particles of light
FOXO4-DRI breaks the bond between FOXO4 and p53, senescent cells die off. Symbolic image.

What you need

Supplies

2 things, numbered as in the picture

Tick off what you already have. Vial and BAC water are our real shop photos at the same size.

FOXO4 vial and bacteriostatic water at the same size with the black TPD label, next to two U-100 insulin syringes, two alcohol swabs and a sharps container with a blue lid

  1. FOXO4-DRI vial

    The FOXO4-DRI vial (lyophilized powder).

    In the shop

  2. Water and supplies

    Bacteriostatic water, U-100 insulin syringes, alcohol swabs.

    In the shop

Reconstitution

Use the peptide calculator. A 10mg vial with 2ml water gives 5mg per ml. Just add the water to the vial and let it dissolve.

Step by step

Dissolving the powder

Four steps, the same for every vial size.

  1. 1Wipe the cap

    Clean the rubber stopper with an alcohol swab.

  2. 2Add BAC water

    Just add it, it does not matter if it hits the powder directly.

  3. 3Swirl or shake

    Until everything has dissolved, both are fine.

  4. 4Draw up

    With the U-100 insulin syringe.

Less water higher concentration fewer units on the syringe Example: 10 mg + 2 ml = 5 mg/ml

Dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts

Injection

The injection is subcutaneous, into the fat layer under the skin. Common spots are the abdomen (keep about two finger-widths clear of the navel), the front and the inner side of the thigh, or the back of the upper arm.

The short version:

Injection

Where and at what angle

Pick a spot or switch the angle. Subcutaneous means: into the fat layer, not the muscle.

Rotate the spot each time, never the same one twice in a row.

90°More fat under the skin

Rule of thumb: where there is more fat under the skin, insert straight at 90 degrees. In lean people with little fat, 45 degrees, so the needle stays in the fat layer. Simplified diagram.

  1. Clean the spot with an alcohol swab and let it dry

  2. Pinch up a small fold of skin

  3. Insert the needle: at 90 degrees where there is more fat under the skin, at 45 degrees in lean people with little fat

  4. Inject slowly, wait a moment, then withdraw

  5. Put the needle straight into the sharps container

Rotate the site each time so the tissue does not get irritated. Never the same spot twice in a row.

What the research shows

A widely noted study (Baar, Cell 2017) showed that FOXO4-DRI removed senescent cells in aged mice and restored fur density, kidney function and fitness. The study does not report a longer lifespan. That is an impressive animal result and an interesting mechanism, but there are no human studies. FOXO4-DRI is clearly experimental.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

How selectively FOXO4-DRI hits old cells1

Effect on senescent versus normal cells, as a multiple

Human lung fibroblasts (IMR90)1 Cell viability after treatment
With FOXO4-DRI 11.7-fold

According to the full text an 11.73-fold difference. The same peptide chain made of normal L-amino acids had no effect, so the D-retro-inverso form is what matters. Cell culture only.

Cell death in old Leydig cells3

Share of dying cells in percent, aged mouse cells

Aged Leydig cells3 Cell culture (TM3)
Without FOXO4-DRI (comparison) 10%
With FOXO4-DRI 27%

Values from the full text. Normal Leydig cells showed no measurable harm. In mice aged 20 to 24 months blood testosterone rose. Not tested in humans.

Two spheres on a bright lab bench: one grey and cracked, one clear and glowing, petri dishes beside them
The results come from aged mice, there are no human studies. Symbolic image.

Research status

Where the research stands

Where the compound stands on the way from lab research to approval. As of 26 Oct 2026. 6

  1. Preclinical Cell assays and mouse models
  2. Phase 1 no registered trial
  3. Phase 2 no registered trial
  4. Phase 3 no registered trial
  5. Approval not yet
Not approved and no registered human trial. FOXO4-DRI has only been studied preclinically so far.6

So far there is no registered trial in humans. 6

Side effects

  • Solid human data are missing.
  • A compound that specifically pushes cells into death is not harmless, particular caution.
  • Local reactions at the injection site.

Storage

Before mixing the powder is robust, normal room temperature (around 20 to 25 degrees) is fine, ideally kept in the dark. After mixing, keep in the fridge (2 to 8 degrees), do not freeze. It stays good there for at least 4 to 6 months with barely any loss of potency, in practice considerably longer. Swirl or shake to mix, both are fine.

Shelf life

How long it keeps

Undissolved (powder) Room temperature, around 20 to 25 degrees, dark

Robust, no fridge needed.

Dissolved (mixed) Fridge, 2 to 8 degrees, do not freeze

At least 4 to 6 months with barely any loss of potency. The bacteriostatic water brings a preservative.

  • Keep it dark
  • Dissolved: 2 to 8 degrees
  • Note the mixing date on the vial
Nine vials with white powder and blue caps in the door shelf of a bright fridge
Powder dark at room temperature, once dissolved into the fridge (2 to 8 degrees), stable there for at least 4 to 6 months. Symbolic image.

Related

Related compounds

A different path: all in the TPD lexicon.

FOXO4-DRI
Epitalon Different approach: telomeres instead of old cells MOTS-c Different approach: mitochondrial metabolism SS-31 (Elamipretide) Different approach: protecting the mitochondria Humanin Different peptide from ageing research NAD+ Inject Different approach: coenzyme of cell metabolism

FAQ

Common questions about FOXO4-DRI

Short answers, each backed by the sources below.

Is FOXO4-DRI approved or studied in humans?

No. There is no approval and as of 26 October 2026 ClinicalTrials.gov lists not a single trial with FOXO4-DRI. All data come from cell experiments and mouse models.6

How does FOXO4-DRI work?

Senescent cells survive because the protein FOXO4 holds the guardian p53 in the nucleus. FOXO4-DRI binds to p53 and displaces FOXO4, as structural data from 2025 show. p53 then leaves the nucleus and the cell undergoes programmed cell death. In cell culture this hit old fibroblasts 11.7 times more strongly than normal ones.12

What did the 2017 Cell study show?

In mice FOXO4-DRI dampened the damage caused by the cancer drug doxorubicin. In fast-ageing and naturally aged mice fitness, fur density and kidney function came back. Platelets stayed unchanged. The study does not report a longer life span.1

What further findings are there?

In aged mouse Leydig cells the share of dying cells rose from 10 to 27 percent, in old mice blood testosterone rose. In long-expanded human cartilage cells FOXO4-DRI removed more than half of the cells, but the newly formed cartilage was not better.34

Is removing old cells harmless?

Not necessarily. A 2023 study removed old cells in mouse models of pulmonary hypertension, also with FOXO4-DRI. Cells of the lung vessels were lost and the pulmonary hypertension got worse. So senescent cells can also have a job to do.5

What does DRI mean?

D-retro-inverso: the chain is made of D-amino acids in reverse order. That way it resembles the original in shape but is harder to break down. The same chain made of normal L-amino acids had no effect in cell culture.1

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

Apoptosis
Programmed cell death: the cell dismantles itself in an orderly way without causing inflammation.
D-retro-inverso
A peptide built from D-amino acids in reverse order. It is broken down more slowly in the body.
FOXO4
Protein in the nucleus that is increased in senescent cells and holds on to p53.
Leydig cells
Cells in the testes that make testosterone.
Lyophilisate
Freeze-dried powder. Without water a peptide keeps much longer.
p53
Guardian protein of the cell. With severe damage it stops division or triggers programmed cell death.
Preclinical
Research before first use in humans, in cell cultures and animal models. Results cannot be transferred directly to humans.
Senescent cells
Aged cells that no longer divide but do not die either. They release inflammatory substances and accumulate with age.
Senolytic
A substance that selectively makes senescent cells die.
Subcutaneous
Into the fat layer just under the skin.

Evidence

Sources

Show all 7 sourcesHide sources 5 Studies1 Trial registry1 Database checked 26 Oct 2026

Studies

  1. FOXO4 peptide removes senescent cells in old mice

    Baar et al., Cell, 2017

    DOI 10.1016/j.cell.2017.02.031 PMID 28340339
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PMC (Volltext)
  2. Structure of FOXO4-DRI binding to p53

    Bourgeois et al., Nature Communications, 2025

    DOI 10.1038/s41467-025-60844-9 PMID 40593617
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. Old Leydig cells and testosterone in old mice

    Zhang et al., Aging, 2020

    DOI 10.18632/aging.102682 PMID 31959736
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PMC (Volltext)
  4. Removing old cells from human cartilage cell cultures

    Huang et al., Frontiers in Bioengineering and Biotechnology, 2021

    DOI 10.3389/fbioe.2021.677576 PMID 33996787
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  5. Removing old cells can worsen pulmonary hypertension (mice)

    Born et al., Circulation, 2023

    DOI 10.1161/CIRCULATIONAHA.122.058794 PMID 36515093
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed

Trial registry

  1. Search on ClinicalTrials.gov (no trial with FOXO4-DRI)

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. FOXO4-DRI in PubChem

    PubChem, U.S. National Library of Medicine (CID 167312269)

    Checked 26 Oct 2026 via PubChem

In the shop

FOXO4-DRI in the catalog

Sizes, prices and shipping times are on the product page.

To the product