FOXO4-DRI is an experimental peptide designed to make senescent cells, sometimes called “zombie cells”, destroy themselves. In a landmark 2017 mouse study it improved fur, fitness and kidney function in old mice.[1] It has never been tested in people, and it is not approved for any use.[14]

This profile covers how FOXO4-DRI works, the mouse and cell research, how it compares with senolytic drugs that have reached human trials, what is known about safety, and its legal and anti-doping status.

What is FOXO4-DRI?

FOXO4-DRI was designed by Peter de Keizer and colleagues at Erasmus University Medical Center in Rotterdam, with collaborators including Judith Campisi at the Buck Institute.[1]

The name describes how it is built:

  • FOXO4 is the protein it copies. The peptide is based on a part of FOXO4 that is the same in humans and mice.[1]
  • DRI stands for D-retro-inverso. The peptide is made of mirror-image (D) amino acids in reverse order, a design that resists breakdown in the body. The same peptide made of normal (L) amino acids did not kill senescent cells.[1]
  • It is joined to a short sequence from HIV-TAT, a cell-penetrating tag that helps it get inside cells.[1]

FOXO4-DRI is a senolytic: a treatment that selectively removes senescent cells.

How FOXO4-DRI works

Senescent cells have stopped dividing after damage, but they resist dying. They release inflammatory signals (the senescence-associated secretory phenotype, or SASP) that may harm nearby tissue as we age.[1]

De Keizer’s team found that in senescent cells, FOXO4 binds the tumor-suppressor protein p53 and keeps it in the nucleus, which stops p53 from triggering cell death. FOXO4-DRI competes with FOXO4 for p53. Once released, p53 moves out of the nucleus and the senescent cell undergoes apoptosis (programmed cell death).[1][2]

In lab dishes, FOXO4-DRI was about 11.7 times more potent against senescent human fibroblasts than against normal ones.[1] A 2025 structural study from Austria and the Netherlands showed exactly where FOXO4-DRI binds p53.[3]

FOXO4-DRI research: what studies have found

The 2017 Cell study (mice)

Baar and colleagues tested FOXO4-DRI in three mouse models:[1]

  • Chemotherapy damage: in mice given doxorubicin, FOXO4-DRI reduced senescent cells and countered the drug’s weight loss and liver damage.
  • Fast aging: in XpdTTD/TTD mice, which model a human premature-aging syndrome, it improved fur density, responsiveness, running-wheel activity and kidney function.
  • Natural aging: in mice over 110 weeks old, it lowered plasma urea and creatinine (signs of better kidney filtering) and improved fur density.

Later animal studies

  • Testosterone: a Chinese study found that FOXO4-DRI cleared senescent testosterone-producing Leydig cells and eased age-related testosterone decline in naturally aged mice.[4]
  • Blood vessels: another Chinese team reported better aortic function and fewer senescent blood vessel cells in naturally aged and fast-aging mice.[5]

Human cells in the lab

In human cartilage cells grown in a dish for transplant, FOXO4-DRI removed more than half of the heavily expanded (more senescent) cells while sparing early-stage cells.[6] This is lab work, not treatment of people.

In people

There are no human studies of FOXO4-DRI. As of October 2026, no trial is registered on ClinicalTrials.gov.[14]

De Keizer co-founded Cleara Biotech to develop the approach. A Lifespan Research Institute profile of the company, last updated in September 2025, relays Cleara’s own account: its lead compound is a newer FOXO4-based peptide, CL04183, rather than FOXO4-DRI itself; its first planned use is in therapy-resistant cancers; and the company says it completed GLP toxicology studies in rats and non-human primates in 2025 while preparing a clinical trial application to FDA.[8] We found no registered or published clinical trial of any Cleara compound.

Senolytics in humans: the wider picture

Other senolytics have reached small human trials, which gives useful context:

  • Lung fibrosis (2019): in an open-label pilot of 14 people with idiopathic pulmonary fibrosis, dasatinib plus quercetin (D+Q) improved walking distance and gait speed, but lung function did not change.[9]
  • Bone (2024): in a phase 2 randomized trial of 60 postmenopausal women, D+Q did not change the main bone-loss marker at 20 weeks.[10]
  • Fatty liver (2026): in a randomized trial of 31 people with fibrotic MASH, liver fibrosis improved in 47% on D+Q versus 7% on placebo. Side effects were more common with D+Q (82% versus 43%) but went away on their own.[11]

A 2026 systematic review concluded that senolytics remain investigational, with evidence insufficient to establish clinical benefit or long-term safety.[12]

FOXO4-DRI side effects and safety

Human side effects are unknown.

  • Mouse tolerability: in the 2017 study, it was well tolerated at the doses used and did not noticeably change platelet counts, a problem seen with some other senolytics.[1]
  • Clearing senescent cells is not always helpful: a French-led study found that removing senescent cells, including with FOXO4-DRI, worsened pulmonary hypertension in mouse models.[7]
  • p53 is a cancer-control protein: FOXO4-DRI works by changing how p53 behaves. Long-term effects of this in people are unknown.
  • Product quality: FOXO4-DRI sold online is not made to drug-quality standards, so purity and dose are unknown.

FOXO4-DRI dosage: what has been studied

No human dose exists. In the main mouse experiments, mice received 5 mg/kg three times, every other day, injected into a vein or the abdominal cavity.[1] Mouse doses cannot be converted directly into a safe or effective human dose.

FOXO4-DRI vs epitalon and MOTS-c

  • Epitalon is a four-amino-acid peptide from Russian anti-aging research, studied mainly for effects on telomeres. It is not designed to target senescent cells.
  • MOTS-c is a peptide made by mitochondria, studied for metabolism and exercise capacity.
  • FOXO4-DRI is the only one of the three designed to remove senescent cells.[1]

See our longevity peptides overview for the evidence on other compounds.

  • Not approved anywhere. FOXO4-DRI is a preclinical research compound with no approved medical use and no registered human trials.[14]
  • Anti-doping: WADA’s 2026 Prohibited List does not name FOXO4-DRI. Section S0 bans at all times any pharmacological substance not covered elsewhere on the list that has no current approval for human therapeutic use.[13] In our reading it falls under S0.

We did not find trustworthy, non-vendor user reports about FOXO4-DRI, so this profile does not include a user-experience section.

This is general information, not legal or medical advice.