Peptide Profile
FOXO4-DRI
A senolytic peptide that clears aged "zombie" cells to support healthy aging — run in short, cycled courses a few times a year.
Compound Profile
Scientific & Efficacy Data
C228H388N86O64
Molecular Formula
5358 g/mol
Molecular Weight
Not formally established in humans; the D-retro-inverso design resists enzyme breakdown, giving longer stability than ordinary L-peptides
Half-Life
Not established; animal studies used intraperitoneal injection. Oral bioavailability is not established
Bioavailability
2460055-10-9
CAS #
167312269
PubChem ID ↗
Developed By · 2017
Marjolein Baar, Peter L.J. de Keizer and colleagues
Erasmus University Medical Center, Rotterdam, Netherlands
Primary Benefits
Its standout, well-replicated effect in the lab: selectively removing zombie cells. It cut senescent human cells from over 40% to under 5% in culture [2] and cleared them in aged mice [1].
In mice, clearing zombie cells translated into real tissue gains: regrown fur, better kidney function, and improved fitness [1], plus healthier blood vessels [3].
It largely spares healthy cells, because they do not depend on the FOXO4–p53 trick to survive [1]. This selectivity is a big reason it is so studied.
Amino Acid Sequence
LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRP (D-retro-inverso: reversed sequence built from D-amino acids)Dosing
How much
do I take?
Timing
Best time to take
Morning is most common. Because FOXO4-DRI is cycled in short bursts rather than taken daily, exact time of day matters less than sticking to your every-other-day or 5-on/2-off schedule.
With food?
Food does not matter — it is injected under the skin, not swallowed, so it works the same whether you have eaten or not.
If stacking
Run FOXO4-DRI as its own short cycle. Many people pair senolytic cycles with healthy-aging basics like NAD+ precursors, spermidine, or fisetin between cycles, but keep other senolytics out of the same cycle so you can judge how you respond.
Adjusting Your Dose
Increase if
- +You tolerated a starting cycle well with no strong reaction
- +You have higher body weight and are moving toward the weight-based protocol
- +Your goal is clearing a heavier senescent-cell burden
Decrease if
- -You feel notably run-down, flu-like, or fatigued during a cycle
- -You get strong injection-site reactions
- -You are new to senolytics and want to ease in
Signs of right dose
- ✓You get through a cycle with only mild, short-lived fatigue
- ✓Improved energy, recovery, or skin quality in the weeks after a cycle
- ✓No lingering side effects between cycles
Dosing Calculator
Calculate Your Exact Dose
Step 1: Peptide Weight
Find the weight printed on your peptide vial label
Look here!
The peptide weight is printed on the label
Look here!
The weight is on the label
Suitability
Is this
right for me?
Best For
Senescent ("zombie") cell research
FOXO4-DRI is one of the best-studied tools for selectively clearing senescent cells in the lab. In aged mice and in human cells grown in a dish, it removed these worn-out cells while leaving healthy ones largely alone [1][2].
Healthy-aging and tissue-function research
In its first study, aged mice regained fur density, kidney function, and physical fitness after treatment [1]. Later work showed renewed blood-vessel cell function and less artery stiffness in animals [3]. This makes it a key research compound for understanding how clearing old cells affects whole-body aging.
Mechanism and drug-design research
Because scientists have mapped exactly where it binds p53 [5], FOXO4-DRI is valuable for studying the FOXO4–p53 survival pathway and for designing future senolytic drugs.
Consider Alternatives If
Goal: Senescent cell clearance research
Consider: Dasatinib + Quercetin (D+Q), Fisetin
Goal: Healthy-aging research with more human data
Consider: Fisetin, Spermidine, NAD+ precursors (NMN, NR)
Who Should Avoid
Do not use if
- ×You have active or recent cancer
- ×You are pregnant or breastfeeding
- ×You are under 18
- ×You want a proven, approved, human-tested treatment
Use with caution if
- !You take any medication affecting the p53 or apoptosis pathways
- !You have a chronic illness and no physician oversight
- !You are considering combining it with other senolytics
Administration
How do I
use it?
Reconstitution
What you need
- •Bacteriostatic water for injection
- •Alcohol swabs
- •A sterile syringe for mixing
- •Insulin syringes for dosing
- •Your FOXO4-DRI vial
Injection
Route
Subcutaneous — a small injection into the fat just under the skin, using an insulin syringe.
Best sites
- •Lower abdomen (about 2 inches from the navel)
- •Love handles / flank
- •Upper outer thigh
Technique
- 1.Swab the site with alcohol and let it dry
- 2.Pinch a fold of skin and insert the short insulin needle at about 45–90 degrees
- 3.Push the plunger slowly and steadily
- 4.Release the skin and remove the needle
- 5.Rotate sites each dose to avoid soreness
Storage
Signs of degradation
Safety
Is it
safe?
Safety Profile
FOXO4-DRI is generally run in short, spaced-out cycles, which keeps exposure low. The most common experiences are mild and short-lived: some tiredness or a flu-like feeling for a day or two during a cycle as your body clears dead cells, plus the usual minor injection-site soreness. The one real precaution worth taking seriously: because it activates p53, the protein that guards against cancer, anyone with active or recent cancer should only use it under an oncologist's care. If you are pregnant, breastfeeding, or under 18, skip it.
The strongest evidence comes from animal and human-cell studies [1][2][3], and people use cycled protocols scaled from that research. Source the peptide from a reputable supplier and confirm purity.
Common Side Effects
Experienced by some users
Temporary tiredness during a cycle
The most common thing people notice is feeling a bit run-down or flu-like for a day or two during a clearance cycle. This is thought to be your body clearing out and cleaning up dead senescent cells.
Management: Rest, stay hydrated, and keep doses spaced (every other day). If it is strong, drop to the lower 1 mg starting protocol next cycle.
Less Common
- •Injection-site reactions
These typically resolve with continued use or dose adjustment.
Stop and Seek Help If
- ×Any signs of an allergic reaction (hives, swelling, trouble breathing)
- ×New or unusual pain, lumps, or unexplained symptoms
- ×A new cancer diagnosis or cancer treatment starting
- ×Any reaction at the injection site that worsens
- ×Simply feeling unwell after use
FOXO4-DRI is a cycled senolytic. Stop a cycle if you feel notably unwell and pick it back up when you recover. If you have a medical condition, loop in a knowledgeable healthcare provider.
Interactions
With other peptides
- !Combining multiple zombie-cell-clearing agents at once has not been studied for safety and could add up unpredictably.
With medications
- !Cancer treatments / chemotherapy - FOXO4-DRI acts on the p53 pathway that cancer therapies also target; combining them is uncharacterized and potentially risky. Oncologist oversight is essential.
- !Any prescription medication - No human interaction studies exist. Interactions cannot be ruled out.
With supplements
- ✓Supplements in general - No interaction data exists. Because human use is experimental, no supplement combination can be called proven safe.
Effectiveness
Does it
work?
Evidence Level
Preclinical only — animal and cell-culture studies; no human trials
What to Expect
How a cycle works
What you might notice
- •You run a short course — either 3 doses over a week, or 5-on/2-off for two weeks
- •Then you stop and let your body finish the cleanup
What's normal
- •Senolytics work in bursts, not as a daily build-up
- •A little fatigue during the dosing days is common
What's next
- →Wait 4–6 months, then repeat the cycle 2–4 times per year
Hours to days (lab and animal studies)
What you might notice
- •In cells, the self-destruct program in zombie cells switched on within hours of exposure [1]
- •Senescent cells began to be cleared during the short dosing course
What's normal
- •Senolytics act in quick bursts, not slow daily build-up
- •Effects in dishes happen faster than anything would in a whole body
What's next
- →In studies, a short course was followed by a rest period rather than continuous dosing
Weeks (animal studies)
What you might notice
- •Aged mice regained fur density, kidney function, and physical fitness over the weeks after treatment [1]
- •In vessel-aging studies, artery stiffness and aging markers dropped over about a month [3]
What's normal
- •Tissue-level improvements in animals took days to weeks to appear
- •Results varied by tissue and by study
What's next
- →These remain animal findings; whether anything similar occurs in humans is unknown
Signs It's Working
Laboratory markers (research)
- ✓Fewer SA-β-gal positive (senescent) cells [2]
- ✓Lower aging markers p16 and p21 [3]
- ✓Less DNA-damage signal (gamma-H2AX) [3]
- ✓Higher apoptosis signals: BAX and cleaved caspase-3 up, BCL-2 down [3]
Animal/physical outcomes (research)
- ✓Regrown fur density in aged mice [1]
- ✓Better kidney function [1]
- ✓Improved running endurance and grip strength [1]
- ✓Reduced artery stiffness [3]
What people report after a cycle
- ✓More energy and better recovery in the weeks following a cycle
- ✓Improvements in skin quality and tone
- ✓Better joint comfort and mobility
- ✓A general sense of "feeling younger" between cycles
Not Seeing Results?
Common reasons
- •Dose too low for your body weight — move toward the weight-based mg protocol
- •Cycles spaced too far apart — most people run 2–4 cycles per year
- •Product quality or purity issues — use a reputable supplier
- •Expecting overnight changes — benefits build over the weeks after a cycle
- •Skipping the basics — sleep, training, and nutrition still drive most of the results
Key Research
[1]"Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging"
Baar MP, Brandt RMC, Putavet DA, et al., 2017
Finding: The foundational study. The researchers designed FOXO4-DRI to break the FOXO4–p53 link that keeps senescent cells alive. In mice, it selectively killed senescent cells, neutralized doxorubicin (chemotherapy) toxicity, and restored fitness, fur density, and kidney function in both fast-aging and naturally aged mice.
View Study[2]"Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes"
Huang Y, He Y, Makarcyzk MJ, Lin H., 2021
Finding: In human cartilage cells (chondrocytes) grown and expanded in the lab, 25 micromolar FOXO4-DRI for 5 days cut the share of senescent (aged) cells from over 40% to under 5%, while leaving minimally aged cells unharmed.
View Study[3]"FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway"
Hu et al., 2025
Finding: In blood-vessel lining cells and in mice (5 mg/kg by intraperitoneal injection every 2 days for one month), FOXO4-DRI lowered aging markers (p21, p16, gamma-H2AX), raised BAX and cleaved caspase-3 while lowering BCL-2, restored vessel-cell tube formation and migration, and reduced artery stiffness and inflammation.
View Study[4]"FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation"
Communications Biology (Nature Portfolio), 2025
Finding: In keloid scar cells, FOXO4-DRI triggered death of senescent fibroblasts by pushing phosphorylated p53 (at serine 15) out of the nucleus, supporting a possible role in scar-related research.
View Study[5]"The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI"
Nature Communications, 2025
Finding: Using structural biology, researchers showed that both FOXO4 and FOXO4-DRI bind the flexible (disordered) transactivation region of p53 — pinpointing exactly where the peptide acts.
View StudyFrequently Asked Questions