★ Metabolic Longevity

FOXO4-DRI

Metabolic Longevity · 10mg × 10 vials

In plain terms: FOXO4-DRI is a research compound - oral, fast-acting and well studied.

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Quick Start
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Format
Injectable (reconstituted) · 10mg × 10 vials
🎯
Who it's for
aggressive longevity
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How it's run
2.5 mg SubQ per injection (half a 5 mg vial), three injections spaced 4 days apart, one full cycle
When you'll notice
senescent-cell clearance signaling begins within the first 3-dose pulse; subjective effects (energy
Pricing
$450from · kit of 10
US: 2-5 day · Intl: 7-14 day
+ $40 ship · singles $20 · free over $1k per tier
10mg × 10 vials$450
Order / Consult on Telegram →
short (peptide cleared within minutes to a few hours; downstream pro-apoptotic signaling in senescent cells unfolds over 24-72 hours per dose)
Half-life
pulse (3-dose cycle / quarterly cadence)
Cycling
senescent-cell clearance signaling begins within the first 3-dose pulse
First effects
metabolic-longevity
Class
Overview

What Is FOXO4-DRI?

FOXO4-DRI is a D-retro-inverso peptide built from a fragment of the FOXO4 transcription factor sequence, reverse-engineered with D-amino acids so it resists protease degradation and reaches its target intact. In senescent cells (cells that have stopped dividing but refuse to die, accumulating with age and pumping out inflammatory signals known as SASP), FOXO4 normally binds p53 in the nucleus and holds it there, blocking p53's natural job of triggering apoptosis. FOXO4-DRI is a competitive disruptor: it muscles into the FOXO4-p53 binding interface, releases p53 back into the cytoplasm/mitochondria, and lets p53 do what it would have done in a young cell, which is push the senescent cell into programmed cell death. Healthy non-senescent cells aren't relying on a FOXO4-p53 trap to survive, so they're left untouched. The result, in the 2017 Cell paper that put this peptide on the map (de Keizer / Baar et al, Buus Lab), was selective senolysis: in aged and chemo-aged mice, three pulse doses cleared p16-positive senescent cells from kidney, liver, muscle, and skin, restored kidney function, brought back fur density on bald patches, and roughly doubled running endurance on a treadmill compared to age-matched untreated controls. The "old mouse to young mouse" before/after photographs from that paper, with the bald grey mouse regrowing a full coat after three doses, are what drove FOXO4-DRI into the longevity research community in the first place.

There is currently zero human RCT data. Every efficacy and safety claim above is mouse, in vitro, or single-subject anecdote. This is the most experimental compound on the catalog.

Protocols

Typical dose ranges by experience level - educational reference. Message us and we tailor it to you.

Protocol2.5 mg SubQ per injection (half a 5 mg vial), three injections spaced 4 days apart, one full cycle
Frequency3 doses per cycle, 1 cycle then assess
DurationA single beginner cycle is 9 days (day 0, day 4, day 8), followed by a 12+ week observation window before considering another cycle

First-cycle users should plan the three injection days on a low-stress weekend / off-work window. The 2017 mouse data showed transient lethargy in the first 24-48 hours post-dose, and self-experimenter reports echo this in humans (fatigue, mild fever feeling, occasional headache). This is not a "feel great immediately" peptide. The expected payoff is downstream, 4-8 weeks after the cycle completes, as inflammation drops and the body stops carrying the SASP burden from cleared senescent cells.

Protocol5 mg SubQ per injection (full 10 mg vial reconstituted at 5 mg/ml = 1 ml = full single dose; one vial per injection), three injections spaced 4 days apart
Frequency3 doses per cycle (day 0, day 4, day 8), repeat quarterly (every ~3 months) or biannually
DurationEach cycle is ~9 days of active dosing followed by 11-24 weeks off. Most intermediate protocols settle at 2-4 cycles per year.

This is the most-cited community protocol and the one closest to scaled-up mouse dosing (the de Keizer paper used 5 mg/kg in mice spread across three doses; the 5 mg human dose is an empirical floor, not an allometric conversion). One 10 mg kit (10 vials) gives ~3 full cycles at 5 mg per injection, which lines up cleanly with a yearly quarterly schedule. Pair with an NAD+ pulse the week after the cycle ends to support regenerative signaling in the cleared tissue niches.

Protocol5 mg SubQ per injection, three injections spaced 4 days apart, with stack layering (Epithalon, NAD+, BPC-157)
FrequencyQuarterly cycling, four cycles per year
DurationSustained year-over-year quarterly cycling is the most aggressive published community pattern. There is no human trial defining a ceiling, and there is no safety data past mouse studies, so "advanced" here means a layered longevity program, not higher individual doses.

Advanced users almost always run FOXO4-DRI inside a broader longevity program (Epithalon 10-20 day pulse twice yearly, NAD+ weekly maintenance, GHK-Cu, possibly thymalin / thymosin alpha-1). The senolytic clears the cells, the regenerative stack rebuilds the tissue niche, and the immune-modulating layer reduces re-accumulation. Running FOXO4-DRI alone every quarter without a regenerative follow-up is leaving the second half of the protocol on the table.

What To Expect
senescent-cell clearance signaling begins within the first 3-dose pulse
noticeable change
subjective effects (energy
noticeable change
sleep
noticeable change
recovery
noticeable change
Side Effects

Straight talk - what people actually report, and what the studies measured.

What users report
From forums, Discord & TikTok
  • Post-injection fatigue / "flu wave": most-reported acute effect, 24-48 hours post-each-dose, described as low energy, mild body ache, occasional low-grade temperature. Resolves before the next dose. Believed to be the inflammatory wave from clearing the SASP burden.
  • Headache: moderately common in the 24 hours after the first dose of a cycle, usually milder on doses 2 and 3.
  • Local injection-site irritation: redness, transient itch, occasional welt at the SubQ site, more pronounced because of the relatively large 1 ml volume. Splitting into two 0.5 ml injections reduces this.
  • Mild nausea: occasionally reported, usually on the first dose.
  • Energy / sleep improvement: most-reported delayed effect, typically described 3-6 weeks after cycle completion. Some users report better recovery from training, calmer mood, less morning stiffness.
  • Hair / skin changes: occasional anecdotal reports of hair regrowth on thinning crowns and skin smoothness, almost always when stacked with GHK-Cu and not from FOXO4-DRI in isolation. The mouse-paper fur regrowth photos drive expectations that solo FOXO4-DRI rarely matches in humans.
  • Unknown long-term: every honest community write-up flags this. No human safety follow-up past a few self-experimenter cycles. Theoretical risks include off-target apoptosis under stress, immune effects, and unknown cancer-surveillance interactions. Run at your own risk is the standard community caveat.
  • - Divergence: There is no RCT to diverge from. Every "clinical" claim about FOXO4-DRI in humans is community / self-experimenter data extrapolated from mouse work. Customers should be told this directly, not sold on it as established.
What the studies show
Measured in clinical trials
  • No human RCT data exists. The 2017 Cell paper (Baar et al, de Keizer lab) reports no overt toxicity in aged and chemo-aged mice across three pulse doses, with no weight loss, no organ damage on necropsy, and no behavioral changes outside the expected post-dose lethargy. Follow-up work in mouse models of pulmonary fibrosis, kidney aging, and chemo recovery has reproduced selective senolysis without observable off-target toxicity, but again, mouse only. No published Phase 1 trial in humans as of 2026.
The Research

Peer-reviewed studies and clinical guidelines - tap any to read the source.

PubMedBaar et al, Cell 2017 - "Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging"

the foundational FOXO4-DRI paper; de Keizer lab; aged + chemo-aged mouse model; fur regrowth, kidney function restoration, treadmill endurance recovery

Read study ↗
PubMedBourgeois & Madl, FEBS Letters 2018 - "Regulation of cellular senescence via the FOXO4-p53 axis"

mechanistic review of the FOXO4-p53 interaction targeted by FOXO4-DRI

Read study ↗
PubMedSenolytic peptide FOXO4-DRI selectively removes senescent cells - review of mechanism and applications

broader review including disease-context senolysis (fibrosis, kidney, hematopoietic stem cells)

Read study ↗
PubMedPharmacological strategies to target cellular senescence

context on FOXO4-DRI's place in the senolytic pharmacology landscape (alongside dasatinib + quercetin, fisetin, navitoclax)

Read study ↗
PubMedSASP and senolytics in aging - mechanistic background

why senescent cell clearance matters as a longevity target

Read study ↗
Physician commentaryPeter Attia podcast / blog - senolytics overview

measured take on senolytics including the FOXO4-DRI mouse data and why human translation is unproven

Read study ↗
+ 2 more studies & references
From The Community

Aggregated sentiment from public forums & socials - real-world reports, not individual endorsements.

Rr/longevity FOXO4-DRI

Post-injection fatigue / "flu wave": most-reported acute effect, 24-48 hours post-each-dose, described as low energy, mild body ache, occasional low-grade temperature. Resolves before the next dose. Believed to be the inflammatory wave from clearing the SASP burden.

Rr/Peptides FOXO4-DRI d

Headache: moderately common in the 24 hours after the first dose of a cycle, usually milder on doses 2 and 3.

LLongeCity senolytic pr

Local injection-site irritation: redness, transient itch, occasional welt at the SubQ site, more pronounced because of the relatively large 1 ml volume. Splitting into two 0.5 ml injections reduces this.

TTikTok longevity

Mild nausea: occasionally reported, usually on the first dose.

Rr/longevity FOXO4-DRI

Energy / sleep improvement: most-reported delayed effect, typically described 3-6 weeks after cycle completion. Some users report better recovery from training, calmer mood, less morning stiffness.

Rr/Peptides FOXO4-DRI d

Hair / skin changes: occasional anecdotal reports of hair regrowth on thinning crowns and skin smoothness, almost always when stacked with GHK-Cu and not from FOXO4-DRI in isolation. The mouse-paper fur regrowth photos drive expectations that solo FOXO4-DRI rarely matches in humans.

Common Questions
SubQ (most common in community use) or IV (per the original mouse protocol, less common in self-experimenters). 2.5 mg SubQ per injection (half a 5 mg vial), three injections spaced 4 days apart, one full cycle
senescent-cell clearance signaling begins within the first 3-dose pulse; subjective effects (energy, sleep, recovery, hair) typically described 4-8 weeks after a completed cycle
Most users run a recovery (PCT) protocol after a cycle to restore natural production and hold onto gains. Message us for the standard protocol.
A popular pairing is FOXO4-DRI + Epithalon (longevity stack). See the Protocols section, or ask us for a stack built around your goal.
Yes. Every batch is third-party lab tested - request the COA on Telegram and we send it over.
Safety & Contraindications

Hard stops

  • Active cancer of any kind. p53 reactivation in cells that have "escaped" normal apoptosis is a theoretical mechanism of tumor suppression, but in the context of an active malignancy with unknown p53 status, dosing FOXO4-DRI is uncharted and high-risk. Wait for remission and physician guidance.
  • Pregnancy, breastfeeding, or actively trying to conceive. Zero reproductive safety data.
  • Active autoimmune flare. The SASP cleanup wave produces transient inflammation that can compound an active flare.
  • Anyone under 30 with no markers of accelerated aging. There is no rationale for senolytic therapy in a young, healthy body where senescent cell load is already low.
  • Acute infection. Senolytic dosing during an active infection has no safety data and the apoptosis cascade overlaps with immune-cell signaling pathways.

Caution flags

  • History of cancer in remission (especially p53-pathway-related cancers; consult before dosing)
  • Active chemotherapy or radiation (although there is mouse evidence FOXO4-DRI helps with chemo-induced senescence, timing is critical and should not be self-managed)
  • Chronic immunosuppression
  • Severe cardiovascular disease (the post-dose inflammatory wave is mild but not zero)
  • Severe renal or hepatic impairment (clearance pathways not characterized in humans)
  • First-cycle users should treat dose 1 like an allergy test, with someone aware and reachable for the first 24 hours

Stacking conflicts

  • Do NOT stack with other unproven senolytics on the same cycle (dasatinib + quercetin, fisetin at senolytic doses); compounding apoptotic signaling without human data is reckless
  • Do NOT run during an active BPC-157 / TB-500 healing protocol for a fresh injury (the apoptosis signal counters the regenerative signal at the local tissue level for the first ~2 weeks; sequence them, don't overlap)
  • Caution with high-dose NAD+ during the active dosing window (day 0-8); NAD+ post-cycle is the protocol, NAD+ same-day is not
Is It Right For You?

✓ Good fit

  • aggressive longevity
  • biological-age-reduction goals
  • post-chemo recovery research
  • 40+ with measurable inflammaging markers
  • customers running a full longevity stack (Epithalon / NAD+ / GHK-Cu)
  • customers who explicitly accept the no-human-data caveat

✗ Not a fit

  • first-time peptide users
  • under-30 healthy users
  • active cancer
  • pregnancy or TTC
  • autoimmune flare
  • customers expecting visible results inside 4 weeks
  • customers wanting a "safe well-studied" longevity option
  • customers unwilling to accept the "mouse data only" framing

Administration & Storage

Route: SubQ (most common in community use) or IV (per the original mouse protocol, less common in self-experimenters)

Injection site: abdomen (SubQ); rotate sites across the three-dose pulse

Storage: refrigerated, use within 7-14 days because of the size of the peptide and its sensitivity; many users reconstitute one vial at a time and use it immediately, treating remaining vials as freeze-dried until needed

Notes: Inject slowly, the volume (1 ml at 5 mg/ml) is large for a SubQ shot and can sting if pushed fast. Some community protocols split the 5 mg dose into two 0.5 ml SubQ injections at separate sites on the same day to reduce local irritation. Keep vials cold and dark; this peptide is more degradation-sensitive than the standard GLP-1 / growth-hormone class. Schedule the three doses 4 days apart on calm days, the systemic apoptosis cleanup can produce a transient fatigue / flu-like wave on day 1-2 post-injection.

All products sold for research purposes only. Not for human or animal consumption. Must be 21 or older to purchase. By placing an order you confirm compliance with all applicable local laws and regulations.