STUDresearch · Peptide
FOXO4-DRI
Also known as
FOXO4 D-Retro-Inverso · FOXO4 DRI · FOX04-DRI · FOXO4DRI · Proxofim (vendor/colloquial discussion) · FOXO4 interference peptide (DRI) · FOXO4 D-retro-inverso peptide · FOXO4-p53 interference peptide
Community talk. May be wrong. Not medical advice. Not a protocol. Not for human or animal use.
Peptide
Some talk
Systemic
SubQ
Senolytic research peptides
Systemic — designed to disrupt FOXO4–p53 survival signaling in senescent cells body-wide after parenteral exposure, not a local injury-site or cosmetic peptide.
What people say
FOXO4-DRI is an experimental D-retro-inverso peptide built to disrupt FOXO4–p53 signaling in senescent cells. The evidence is cell and mouse work, not a human anti-aging trial.
Doses people talk about
Routes, products and schedules differ sharply. The mouse experiment was intraperitoneal, while human reports are uncontrolled and usually subcutaneous.
How it may feel
Reports range from no distinctive systemic feeling to hours of injection-site pain, headache or stomachache. Separate users describe later soreness, skin changes or no clear result; stacks confound attribution.
Recent forum pulse28 mg every 48 h × 3
One author reported hours of site pain after each dose and later skin changes; follow-up bloodwork had not yet been posted.
Lower-mg forum reports3 mg daily × 6; 3 mg EOD × 6
Separate forum users described these finite pulses. One had gonadorelin as a major confounder; the other reported no negative effects.
Foundational mouse exposure5 mg/kg IP
Intermittent efficacy experiments in mice; not a human SubQ equivalence or a dosing interval derived from PK.
Half-life & effect duration
- Half-life in the body
- Half-lifeNo settled estimate
- Felt duration people report
- Acute accountsNo clear systemic effect, or site pain lasting hours / overnight
- Later claimsChanges over days to weeks
Cycles people discuss
Community patterns split between short multi-milligram pulses followed by months off and much longer low-dose ladders. Neither calendar has controlled human validation.
Timing
No measured human or animal parent-peptide half-life was found. A recent report put injection pain in the same-night window, while claimed skin changes appeared about 10 days later; neither establishes clearance.
Stacks
MOTS-c and SS-31 often appear after a FOXO4-DRI pulse, while some users compare it with cheaper D+Q or fisetin. These sequences make later benefits difficult to attribute.
Watch for
Injection-site and systemic symptoms: A recent 3 × 28 mg every-48-hour self-log described significant site pain starting about a minute after each injection and lasting hours, plus intermittent headaches and mild stomachaches that later resolved. Other records mention redness or stinging. These are uncontrolled reports with uncertain product identity.
Tap a line to jump into the full notes. Research only — may be wrong.
Timing context & sources
Half-life in the body
No measured parent-peptide half-life was established in the checked human or animal evidence.
The mouse paper used intermittent efficacy dosing. Community claims of 48–72-hour coverage or years-long benefit are schedule or outcome lore, not plasma measurements.
No human PK study; no reviewed animal concentration-time curve; SubQ product identity and bioavailability are unknown.
- Baar et al. — Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging (opens in a new tab)Article record, abstract and full-paper link; Cell 2017, DOI 10.1016/j.cell.2017.02.031. Mouse and cell efficacy experiments, including intermittent 5 mg/kg exposure; no parent concentration-time PK result was identified in the reviewed article material.Cell and mouse evidence, not human efficacy or safety. Efficacy schedule is not a half-life measurement, and the repository page exposed limited parsed full text.
- FOXO4-DRI: notes from 12 days past 3x 28mg q48h FOXO4-DRI (opens in a new tab)Actual Discourse post stream: researcher6076 posts 1, 4, 7 and 9, Aug. 30–Sept. 2, 2026. Initial report, source survey, product/cost reply and planned day-28 bloodwork timing.One self-experiment, no contemporaneous baseline or published follow-up bloodwork in the inspected thread, unverified product and uncontrolled observations. The author's planned 28-day test does not establish clearance.
Felt duration people report
Acute reports range from no clear systemic effect to site pain lasting hours; later claimed changes appear on a days-to-weeks clock.
One 28 mg report described site pain from about one minute after dosing until before the next morning, with headache and stomachache resolving later. Another user described overnight nodule soreness and substantial co-use.
Single-person reports, different amounts, unverified products and stacks; later skin or mobility changes cannot establish a single-dose effect duration.
- FOXO4-DRI: notes from 12 days past 3x 28mg q48h FOXO4-DRI (opens in a new tab)Actual Discourse post stream: researcher6076 posts 1, 4, 7 and 9, Aug. 30–Sept. 2, 2026. Initial report, source survey, product/cost reply and planned day-28 bloodwork timing.One self-experiment, no contemporaneous baseline or published follow-up bloodwork in the inspected thread, unverified product and uncontrolled observations. The author's planned 28-day test does not establish clearance.
- Any FOXO4-DRI Experiences? (opens in a new tab)Post and visible jet_rodriguez comment/reply sequence: overnight nodule soreness, later mobility and pain claims, and disclosed BPC-157, TB-500, GHK-Cu, TA-1, SS-31, KLOW and MOTS-c co-use.One self-report with extensive sequential co-use, no verified product or objective comparator. Long-term improvement cannot be assigned to FOXO4-DRI alone.
What people say
- Community energy / recovery: Sparse logs of steadier energy, recovery, skin/hair, or “inflammation quieter” — uncontrolled and heavily confounded. forum
- Pain / body feel (anecdote): Isolated Age-Reversal-style reports of widespread pain relief or back-pain change after low-mg use — single-user, not replicated. anecdote
- vs D+Q / fisetin (user talk): Some self-experimenters claim different tissue feel or fewer “hangover” symptoms than small-molecule senolytic pulses; others say outcomes are not better than cheaper D+Q/fisetin and cost much more. forum
- Honest take: No durable measured human benefits in controlled trials; many short runs report nothing noticeable; product identity/purity is a huge confounder on expensive D-synthesis material. forum
- Senescent clearance (preclinical): Selective reduction of senescent-cell viability with healthy cells relatively spared in the foundational culture work. animal
- Aged mice (Baar 2017 Cell): Better running/activity, coat/fur recovery, and kidney function markers in naturally old mice after intermittent FOXO4-DRI. animal
- Chemo recovery models: Faster recovery-type readouts after doxorubicin-style therapy-induced senescence in mice. animal
- Testosterone / Leydig (Zhang 2020 Aging): Clearance of senescent Leydig cells with improved age-related testosterone secretion markers in aged mice. animal
- Spermatogenesis follow-ons: Later mouse work links Leydig SASP reduction to better spermatogenesis readouts after FOXO4-DRI. animal
- Cartilage cells: In vitro expanded human chondrocytes — senescent cells removed without proportional healthy-cell wipeout (Huang 2021). lab
- Pulmonary fibrosis models: Mouse bleomycin fibrosis designs used short 5 mg/kg IP pulses with fibrosis-marker improvements in some papers (e.g., Han 2022-style protocols). animal
- Fitness timeline in mice: Early functional signals often discussed around ~10–14 days (activity, fur), with broader marker shifts over weeks. animal
- Endothelium / vessels: Animal and HUVEC-style work report less endothelial senescence signaling and improved vascular-function framing after FOXO4-DRI (including 2025 endothelial papers). animal
Doses people talk about
- Allometric self-experiment math (Fight Aging): Mouse 5 mg/kg IP ×3 EOD scaled for a ~60 kg human is often guesstimated near ~25 mg per injection IV/IP-equivalent, three alternate-day doses — not a validated human regimen and not proven for SubQ. forum
- Community “full mouse-scale” pulse: Discussed multi-mg SubQ pulses in the ~10–25 mg per pin band, 3 doses every other day (total course often ~30–75+ mg) — cost-prohibitive and purity-sensitive. forum
- “Standard” multi-mg pulse (content guides): Roughly 3–5 mg SubQ every other day × 3 doses, sometimes repeated 1–3× per year. forum
- Conservative multi-mg pulse: Roughly 2–3 mg SubQ every other day × 3 doses as a lower entry before escalating milligrams. forum
- Wide intermittent range (wiki-style community): Research-community writeups span roughly 3–25 mg per injection, EOD for 3–6 doses per cycle, short cycles 1–3×/year. forum
- Ben Greenfield–cited style (secondary): ~3 mg SubQ every other day for six days (three injections), short cycle repeated 1–3×/year — influencer-adjacent, not a trial. forum
- 1 mg community camp: Age-Reversal and similar logs claim meaningful subjective response at ~1 mg SubQ (sometimes on/off over months), arguing mouse-scale 25 mg is unnecessary and unaffordable. anecdote
- 1 mg / 5-on-2-off chart: Some 2026 dosing pages describe 1 mg SubQ morning, 5 days on / 2 off, ~2-week courses, rest 3–6 months, 2–3 courses/year. forum
- Daily mcg ladder (widely copied charts): Weeks 1–4 250 mcg/day SubQ → Weeks 5–8 375 mcg/day → Weeks 9–16 500 mcg/day (sometimes weeks 9–12 and 13–16 both at 500 mcg). forum
- Reddit-style intermediate: Examples include 0.3 + 0.3 + 0.4 mg in first 24 h then 1 mg EOD for ~20 days on 10 mg total, or 2 mg EOD for ~30 days with post MOTS-c talk. anecdote
- Aggressive daily/EOD talk: Some users discuss 10–20 mg per pin over ~10 days (~80 mg course) — contested even inside forums as aggressive given zero human tox data. anecdote
- Route gap: Papers = mouse IP; communities = SubQ; IV appears in experimental/self-experiment scaling talk — bioequivalence unknown. forum
- No human mg/kg standard: Direct mouse→human conversion is discouraged outside research discussion; SubQ bioavailability vs IP is unmeasured in people. forum
- Purity / fill risk: Long all-D peptide is costly to synthesize; under-dosed, wrong-sequence, partial L-isomer, or TFA-salt-heavy product is a recurring community warning. forum
- TFA residual note: Self-experiment literature stresses ordering TFA-exchanged material when custom-synthesizing — residual trifluoroacetate can inflame injection sites. forum
- Framing: Community charts, self-experiment writeups, and preclinical numbers only — not prescriptions, not safety-validated human doses, not medical advice. forum
- High-end forum totals: Reddit-style logs mention full courses on the order of ~80 mg total (e.g., multiple 10 mg vials / ~25 mg ×3 framing) for aggressive experiments. anecdote
- In-vitro working range: Culture work often cites ~25 μM for multi-day exposure; not a body dose. lab
- Mouse gold standard (Baar 2017): ~5 mg/kg intraperitoneal, intermittent (~3×/week or every-other-day pulses) across several weeks in aged / chemo models. animal
- Mouse short pulse pattern: Many later papers reuse 5 mg/kg IP on alternate days for three administrations (e.g., days 1/3/5 or model-specific days 14/16/18 in fibrosis work). animal
- Extended mouse IP: Some aging/endothelium designs use 5 mg/kg IP every 2 days for ~1 month rather than a three-shot pulse. animal
How it may feel
- Hours–day 1: Injection-site awareness ranges from little reaction to substantial pain. One recent 3 × 28 mg every-48-hour self-log described pain beginning about a minute after each injection, lasting for hours and resolving by the following morning, with intermittent headache and mild stomachache during treatment and early recovery. forumanecdote
- Day 1 test-dose lore: Fight Aging–style self-experiment outlines and forum practice often start with a ~1/10 dose day to check acute intolerance before full pulses. forum
- Days 1–3: Some mild flu-like fatigue/malaise or GI unease as apoptotic debris is theoretically cleared; many logs report nothing. anecdote
- vs D+Q hangover: Darren Moore–type writeups and forum discussion note less headache/nausea than dasatinib sessions, sometimes explained as poorer BBB crossing of a large peptide. forum
- Days 3–14: Mouse marker shifts often cited in this window; human subjective change remains inconsistent — expectation bias is high. forum
- Weeks 2–4: Common community checkpoint after a pulse or early ladder weeks — “quieter joints/inflammation,” better recovery, or no change. forum
- Weeks 4–12: Multi-week daily mcg ladders sometimes claim gradual vitality or skin/hair shifts; attribution is weak without biomarkers. forum
- After a short pulse: Mouse logic — benefits may outlast drug exposure until new senescence accumulates; human duration unknown. animal
Cycles people discuss
- Community hit-and-run: Short multi-mg pulse (3–6 injections EOD) then months off; idea is clear a bolus of senescent cells, then let tissue settle. forum
- Yearly frequency talk: Many multi-mg guides frame 1–3 short courses per year with long rests, matching slow re-accumulation lore. forum
- 1 mg course style: ~2 weeks of daily or 5-on/2-off at 1 mg, then 3–6 months off, 2–3×/year. forum
- Daily mcg ladders: ~12–16 week titration pages (250→500 mcg) — long exposure relative to mouse pulses; not trial-validated. forum
- On/off multi-month anecdotes: Some users report taking FOXO4-DRI “on and off for months” at low mg without a fixed published schedule. anecdote
- Re-runs: Months later if subjective benefit faded or new stressors (illness, chemo lore) are thought to rebuild senescence. forum
- Stop / pause talk: Active infection, fresh wounds/surgery, planned major healing, pregnancy/breastfeeding unknowns, active malignancy history, or pulmonary-hypertension concern → communities often pause. forum
- Stack sequencing: Some clear with FOXO4-DRI pulse then follow with MOTS-c / SS-31 / Epitalon “support remaining cells”; others alternate with D+Q or fisetin weeks — no controlled combo schedule. forum
- Animal pulse template: Three (or thrice-weekly) doses over ~1 week, then observe for weeks — the most common published in-vivo pattern. animal
- Animal multi-week intermittent: Several weeks of ~3×/week IP in the original aged-mouse healthspan work. animal
Timing
- DRI persistence lore: Protease resistance → functional story of hours-to-days vs minutes for ordinary L-peptides of similar size. forum
- Practice split: Daily mcg SubQ (steady low exposure) vs intermittent higher pulses (hit-and-run) both exist; no head-to-head. forum
- SubQ vs IP timing: SubQ is assumed slower depot-like absorption than IP/IV bolus — unquantified for this peptide. forum
- BBB / CNS: Large size leads to community claim of limited brain entry (less central “senolytic hangover” than small molecules) — plausible lore, not mapped human PK. forum
- PK gap: No published human plasma half-life, bioavailability, Vd, or clearance study. trial
- No formal animal PK package either: Even mouse work is sparse on measured plasma curves; dosing is efficacy-driven. animal
- 3×/week mouse IP inference: Often read as multi-day coverage per dose (~48–72 h functional window) — inference from schedule, not measured t½. animal
- Downstream cascade: Competitive FOXO4–p53 disruption → p53 release / nuclear exclusion → mitochondrial apoptosis program over hours–days; immune debris/SASP cleanup over days–weeks in narrative timelines. animal
- Mechanistic timeline (extrapolated): Hours = exposure/target engagement; 1–3 days = apoptosis wave; 3–14 days = debris clearance / SASP drop talk; 2–6 weeks = tissue microenvironment improvement in animal framing. forum
- Benefit durability: Mouse improvements can outlast the dosing window until new senescent cells accumulate; retreatment interval in humans is pure guesswork. animal
More on what it is
- Why people care: Longevity circles treat it as the main peptide senolytic after the 2017 Baar et al. *Cell* mouse paper (coat, activity, kidney markers; chemo-recovery models). forum
- Vendor name: “Proxofim” appears on some research-vendor listings for the same senolytic peptide concept — not a distinct clinical brand. forum
- What it is: Synthetic D-retro-inverso (DRI) peptide built to compete with endogenous FOXO4 for p53 binding so senescent (“zombie”) cells lose their apoptosis block and die. Research chemical only — not an approved drug. trial
- DRI design: Mirror-image D-amino acids in reversed sequence resist proteases while preserving a FOXO4–p53-like binding surface; native L-peptides of this size would be chewed up in minutes. trial
- How clearance is supposed to work: Senescent cells upregulate FOXO4, which sequesters p53 in PML nuclear bodies and steers it away from pro-apoptotic programs; FOXO4-DRI displaces that partnership so active p53 can drive intrinsic apoptosis (caspase pathway). trial
- Selectivity claim: In culture, roughly ~10–12× preference for senescent vs control cells in the landmark work (~11.7-fold often quoted) — still cell-model data, not human proof. lab
- Molecule size: Large peptide — secondary sources put MW roughly ~4.8–5.4 kDa and length ~36–48 residues depending on how the full DRI construct is reported; exact catalog identity should be checked against the paper sequence / COA. trial
- Developer context: Erasmus University / de Keizer line of work; Cleara Biotech discussed as a FOXO4-pathway company — development interest is not human efficacy. trial
- Evidence honesty: Mice + cell culture + sparse uncontrolled self-experiment logs; as of mid-2026 no registered human clinical trials on ClinicalTrials.gov and no published human PK/safety package. trial
- Not: Not a GH secretagogue, steroid, proven human anti-aging drug, or interchangeable with dasatinib+quercetin / fisetin / navitoclax. trial
Stacks
- Senolytic rotation: Alongside or alternating dasatinib + quercetin (D+Q) or high-dose fisetin pulses — different mechanisms (kinase/BCL pathways vs FOXO4–p53 peptide). forum
- Don’t combine same-week aggression (caution talk): Some longevity forums warn against stacking multiple strong senolytics simultaneously without spacing — theoretical clearance burden. forum
- Mito adjacency: Often sequenced near MOTS-c or SS-31 (elamipretide) as “clear damaged cells → support remaining mitochondria.” forum
- Epitalon / Epithalon pairings: “Clear senescent cells vs support telomere/pineal narratives in remaining cells” — complementary lore, zero combo RCTs. forum
- Rapamycin adjacency: Same longevity docs and blogs; rapa framed as senomorphic (prevent entry) vs FOXO4-DRI as senolytic (clear existing) — no controlled combo data. forum
- NAD+ / NMN / NR axis: Cellular-energy stacks appear next to FOXO4-DRI in protocol hubs — confounded wellness bundling. forum
- GHK-Cu: Skin/tissue-remodel talk occasionally co-listed in anti-aging peptide menus. forum
- Post-pulse recovery stacks: MOTS-c / SS-31 / sleep / protein after a multi-mg course in anecdote threads. anecdote
- Lifestyle confounders: Sleep, resistance training, metabolic health, and weight loss get credit when “senolytic” outcomes look good. forum
- vs small-molecule cost logic: Many experienced users stick with D+Q or fisetin sessions because FOXO4-DRI multi-mg courses historically cost thousands. forum
Storage notes
- No mix instructions here: STUDresearch does not list reconstitution, diluent volumes, or syringe unit charts. People reconstitute many different ways and vial labels differ — that content creates more confusion than clarity. forum
- Storage (general talk only): Unopened research products are usually kept cool, dry, and away from light per the seller label. Anything after first use is product-specific — follow the label, not a universal forum SOP. forum
Watch for
- Injection-site and systemic symptoms: A recent 3 × 28 mg every-48-hour self-log described significant site pain starting about a minute after each injection and lasting hours, plus intermittent headaches and mild stomachaches that later resolved. Other records mention redness or stinging. These are uncontrolled reports with uncertain product identity. forumanecdote
- Flu-like window: Mild fatigue, malaise, or “under the weather” 1–3 days post-dose in some logs — often blamed on cell-clearance debris. anecdote
- GI: Occasional loose stool, diarrhea, or upset in secondary side-effect lists; poorly quantified. forum
- Immune / clearance burden: Theoretical stress if many cells apoptose at once — reason some prefer spaced pulses over aggressive stacking. forum
- Wounds / surgery / infection: Senescent cells participate in repair and host defense; communities pause near active healing, surgery, or acute infection. forum
- Cancer / p53 complexity: Active cancer or recent cancer therapy is a recurring “don’t self-experiment lightly” flag — p53 and senescence pathways cut both ways (tumor suppression vs SASP). forum
- Selectivity limits: Perfect senescent-only kill is not guaranteed; off-target effects on cells transiently sharing FOXO4/p53 features (including some stem niches) are acknowledged theoretically. forum
- Pregnancy / breastfeeding: No data; apoptosis-inducing research agents are treated as avoid. forum
- Immunocompromised: Debris clearance depends on immune competence — extra caution in community risk lists. forum
- Source / identity risk: Expensive all-D synthesis → mislabel, low purity, incomplete D-substitution, or inactive product; LC-MS identity checks appear in serious self-experiment guides. forum
- Cost-driven underdosing: Users may run mcg ladders that are orders of magnitude below mouse-scaled multi-mg pulses — null results may reflect dose, not mechanism failure. forum
- Senescence surveillance theory: Clearing senescent cells could theoretically remove useful tumor-suppressive senescence signals in some contexts — open scientific debate, not proof of harm. trial
- Pulmonary hypertension (animal red flag): Born et al. 2023 *Circulation* reported that senolytic strategies including FOXO4-DRI aggravated experimental pulmonary hypertension in rodents — important counter-example to “always clear senescence.” animal
- Fibrosis context nuance: Separate mouse fibrosis papers explore FOXO4-DRI as potentially helpful in other lung-injury models — disease-context dependency, not a green light. animal
- No human safety DB: Mouse short-term tolerability ≠ human safety, immunogenicity of D-peptides, drug interactions, or long-term risk. animal
- Regulatory: Not FDA-approved; research-use-only listings; human use is uncontrolled self-experimentation. trial
Evidence mix
Mostly community / anecdote tags
Full: every bullet (trial + community). Use Scan for a faster bro-science read.