Senescence and reproductive aging in experimental models
1Scope of investigation or explicitly identified community interest; not an established indication.
Longevity
FOXO4-DRI
Experimental senolytic peptide
Lab studiesAging cells · reproductive aging1
Investigational; this profile does not establish an approved use.
What does it do?
Experimental senolytic peptide designed to remove senescent cells. Efficacy and safety evidence is preclinical, not demonstrated human rejuvenation.
Approved & studied uses
Community uses Reported, unvalidated
Cellular aging and tissue function
16Mouse/cell senescence and tissue-homeostasis findings.
Inflammation and fibrosis
16SASP reduction and lung-fibrosis models.
Hormonal aging
16Aged-mouse Leydig-cell/testosterone findings.
Chemotherapy injury
16Preclinical toxicity-protection research.
Reasons people report using it; these do not establish benefit.16
Evidence limits
View research →No verified human efficacy or safety trial supports the community injection schedules.1
1 distinct primary sources or abstracts checked. Evidence may concern a parent compound, individual blend ingredient, animal, or cell model; it does not necessarily establish a benefit for this exact product.
Evidence definitions →Key safety information
All risks →Senescent-cell removal
Tissue selectivity and consequences of repeated senescent-cell removal in humans remain unestablished.1
Investigational; this profile does not establish an approved use.
Amino-acid sequence
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An exact sequence has not been verified for this formulation.
Reference identity · not independently confirmed16
Length46 amino acids (D-isoforms)
Molecular weight · Da5,358.2 Da
Formula, sequence notation & identity
D-retro-inverso FOXO4-derived experimental peptide; exact construct must be matched
Sequence and formulation must be confirmed for the exact material; similarly named products are not necessarily interchangeable.
Pep-Pedia identity details
46 amino acids (D-isoforms) · 5,358.2 Da
H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH (all D-amino acids, lowercase denotes D-form)Reference description; checked chemical identity above takes precedence when available.16
Pharmacokinetics
How long does it stay in the body?
Unverified reference estimateNot independently confirmed
Reference half-life1 day – 3 days15
Route / formulationSource page: Injectable. Exact PK route not verified.
This value is reported by a secondary reference. The stated attribution has not been independently verified as a route- and formulation-matched human PK measurement.
50%–79.4%of reference level
Illustrative scenario using an unverified reference estimate. Shading shows the reported half-life range. No midpoint is assumed.
About 3% remaining after 5 d–15 d
Five half-lives in this estimated model. This is not a prediction of when effects stop.
Evidence and model details
Population: Not established by the reference estimate
Source’s stated attribution: Baar et al. 2017 Cell
Source’s reported peak time: 4 hrs. This has not been independently confirmed and is not used in the elimination curve.
100 × 2−time / half-life. Time zero is a reference level, not the moment of administration. Absorption, repeated dosing, metabolites and clinical effects are not modeled. Five half-lives leaves 3.125%, not zero. This curve cannot determine a dosing interval.
What to expect
Study outcomes
Scope of evidence
No verified human efficacy or safety trial supports the community injection schedules.1
Community poll 10 topics · Pep-Pedia snapshot
Voluntary, unverified reports. These percentages do not measure effectiveness or safety.
Experience
Number of responses to this question: not disclosed.
Duration of use
Number of responses to this question: not disclosed.
Primary goal
Number of responses to this question: not disclosed.
Age range
Number of responses to this question: not disclosed.
Gender
Number of responses to this question: not disclosed.
Effectiveness
The source hides 2 additional categories. Their labels and percentages are unavailable.
Number of responses to this question: not disclosed.
How discovered
Number of responses to this question: not disclosed.
Side effects
The source hides 2 additional categories. Their labels and percentages are unavailable.
Number of responses to this question: not disclosed.
Dosage frequency
The source hides 2 additional categories. Their labels and percentages are unavailable.
Number of responses to this question: not disclosed.
Would recommend
The source hides 1 additional categories. Their labels and percentages are unavailable.
Number of responses to this question: not disclosed.
Source & limitations
The source displays “215 responses” for this profile. This is not a confirmed participant count or a denominator for individual questions.
- Voluntary self-reports from Pep-Pedia visitors; identity, treatment, outcomes and timing are unverified. These data are not efficacy or safety estimates.
- The source displays a profile-wide response label, not a confirmed unique participant count. It stays unchanged across questions. Question-specific denominators and absolute option counts are not exposed.
- Only the top five categories are displayed for some questions. Extra categories are retained as an undisplayed-category count; their labels and percentages are unavailable.
- Displayed percentages are rounded. They may not total 100%, especially where categories are hidden.
- This is a dated snapshot, not a live survey or current recommendation.
Protocols
Doses & schedules
Compare purpose, amount, route, frequency, and duration.
Source corrections
Source washout suggestions are unvalidated, not proven safe intervals. Combination labels are hypotheses.
Scroll to compare all columns →
| Route | Dose | Frequency | Goal / evidence | Duration | References |
|---|---|---|---|---|---|
| SubQ | ~25 mg per injection | Every other day × 3 doses (75-100 mg total per cycle) | Anecdotal Human Translation (SubQ)Reference report | 5 days per cycle (3 injections on days 1, 3, 5) | 16 |
Population Population not independently verified; see the reference and linked research. Context Reported in Pep-Pedia’s educational protocol table. Study attribution and applicability to this exact product are not independently established. Source washout suggestions are unvalidated, not proven safe intervals. Combination labels are hypotheses. Source tabs Injectable | |||||
No protocols match these filters.
Study and label doses retain their study context. Reference reports are unvalidated practices, not personal treatment instructions. Ranges remain ranges; escalation stages are labeled.
Reported use periods and breaks. These do not establish a safe cycle or prove that breaks prevent tolerance.
Injectable
- Use period
- 5 days per cycle (3 injections on days 1, 3, 5)
- Break
- Anecdotal protocols suggest monthly cycles
Reported timing
No established optimal timing. Cellular uptake occurs within 2-4 hours, effects persist 72+ hours
Animal and cell protocols 2
Laboratory exposures cannot establish a human dose.
Route
Scroll to compare all columns →
| Route | Dose | Frequency | Goal / evidence | Duration | References |
|---|---|---|---|---|---|
| IV | 5 mg/kg | Every other day × 3 doses | Mouse Research Protocol (IV)Reference report | 5 days per cycle (3 injections on days 1, 3, 5) | 16 |
Population Population not independently verified; see the reference and linked research. Context Reported in Pep-Pedia’s educational protocol table. Study attribution and applicability to this exact product are not independently established. Source washout suggestions are unvalidated, not proven safe intervals. Combination labels are hypotheses. Source tabs Injectable | |||||
| OtherIP | 5 mg/kg | Every other day × 3 doses | Mouse Research Protocol (IP)Reference report | 5 days per cycle (3 injections on days 1, 3, 5) | 16 |
Population Population not independently verified; see the reference and linked research. Context Reported in Pep-Pedia’s educational protocol table. Study attribution and applicability to this exact product are not independently established. Source washout suggestions are unvalidated, not proven safe intervals. Combination labels are hypotheses. Source tabs Injectable | |||||
No protocols match these filters.
Side effects & safety
Senescent-cell removal
Tissue selectivity and consequences of repeated senescent-cell removal in humans remain unestablished.
1Animal-to-human translation
Mouse reproductive findings do not establish a human fertility treatment or safe injection amount.
1Unknown human safety
Repeated-dose immunogenicity and p53/tumor effects unresolved.
Injection reactions
Burning/itching reported; severe reaction, infection, allergy, appetite loss or unusual fatigue warrants evaluation.
Not a complete safety screen. Discuss health decisions with a qualified clinician.
Combinations & interactions
11 entriesCheck cautions and reported pairings. A compatibility claim does not establish that a combination is safe.
Rapamycin
Avoidance reportedSource proposes pathway interference.16
Reference report · Pep-Pedia label: Avoid CombinationQuercetin
Avoidance reportedSource proposes senolytic interference.16
Reference report · Pep-Pedia label: Avoid CombinationDasatinib
Caution reportedUntested sequential senolytics.16
Reference report · Pep-Pedia label: Monitor CombinationCorticosteroids
Avoidance reportedProposed apoptosis interference.16
Reference report · Pep-Pedia label: Avoid CombinationHumanin
Unverified pairingTheoretical protection/clearance pairing.16
Reference report · Pep-Pedia label: CompatibleMOTS-C
Unverified pairingNo interaction studies.16
Reference report · Evidence context: UnknownEpitalon
Unverified pairingNo interaction studies.16
Reference report · Evidence context: Unknown5-Amino-1MQ
Unverified pairingNo interaction studies.16
Reference report · Evidence context: UnknownBPC-157
Unverified pairingNo interaction studies.16
Reference report · Evidence context: UnknownChemotherapy agents
Unverified pairingMouse findings, not clinical guidance.16
Reference report · Pep-Pedia label: SynergisticOther peptides and medicines
Not establishedA controlled interaction assessment for this exact compound and formulation was not identified in the sources checked. Absence of interaction data is not evidence of compatibility.2
Research contextNo matching interactions. Try another name or filter.
Reconstitution
A product-specific preparation or sterility protocol has not been verified.2
Dilution
A concentration calculation cannot establish a suitable diluent, compatibility, storage interval, or sterility. No universal bacteriostatic-water volume is assigned.2
Reference preparation details
Reported handling information, not a validated formulation or instruction to prepare an injectable product.
Injectable
Pep-Pedia describes gentle preparation of a laboratory peptide.
- Solvents mentioned
- Sterile water / Bacteriostatic water
- Reported parameters
- Dry material: reported −20°C. · Prepared solution: reported 2–8°C for 7–10 days.
The source describes gentle mixing and avoiding vigorous shaking.
Appearance & documentation
Appearance and a purity certificate cannot establish sterility, identity, or suitability for injection.
Reported variationNo human clinical trialsReported variationp53 pathway involvementReported variationHigh synthesis costReported concernAvoid with Rapamycin/QuercetinReported appearanceHigh selectivity demonstratedReported appearanceThird-party testing essential
16Available forms
No verified packaging examples included.
Packaging examples, not a market survey. Approved and research products are not interchangeable.
Storage after mixing
Reconstituted research vials
Pep-Pedia reports these handling limits after mixing. They are not validated stability or sterility limits for your vial.
Full storage notes from Pep-Pedia
16Lyophilized: -20°C. Reconstituted: 2-8°C, use within 7-10 days
Storage depends on the formulation, diluent, container, and handling. Follow the specific product label or pharmacist’s instructions.
Research findings
PreclinicalSource context
Source washout suggestions are unvalidated, not proven safe intervals. Combination labels are hypotheses.
Compound identity & other names
FOXO4-DRI is a retro-inverso peptide designed to disrupt FOXO4–p53 signaling in senescent cells. Experimental effects do not establish that removing senescent cells this way is safe or beneficial in people.
Other names: FOXO4 D-retro-inverso
Investigational; this profile does not establish an approved use.
How it may work
Disrupts FOXO4–p53 binding to promote apoptosis in senescent-cell models; selectivity measured in experiments is not a human safety margin.16
Spermatogenesis in aged mice
The paper reported improved sperm-related outcomes in aged mice alongside effects in Leydig cells. It does not establish human fertility or longevity benefits.
1Research areas and evidence gaps
Senescence and reproductive aging in experimental models. Scope of investigation or explicitly identified community interest; not an established indication.1
- No verified human efficacy or safety trial supports the community injection schedules.
- The evidence does not validate the identity, purity or handling of a separately sourced research product.
Community reports Unvalidated
Pep-Pedia reports use in the research-peptide community. These reports are not clinical evidence.2
Community protocol tables are unvalidated descriptions, not treatment instructions.
Search coverage and review status
Additional primary or regulatory sources were checked. No further 2025–2026 exact-compound clinical outcome study was identified in this targeted search; this is not evidence that none exists.
- Checked
- 2026-10-12
- Search
- FOXO4-DRI 2025 2026
- Catalog
- Pep-Pedia ↗ · 12 listed references retained
- Targeted search, not a systematic or exhaustive review.
- Retained bibliography entries marked Bibliography only have not been independently verified.
- Distinct URLs may refer to the same publication; component and formulation boundaries remain important.
AI-prepared summaries. Independent medical editorial review is pending.
References
Original sources and review status. Open a reference to read its summary.
1FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cellsAbstract checked
AI-PREPARED SUMMARY
Senescent Leydig-cell experiments and naturally aged mice showed changes in senescence-associated secretion and spermatogenesis.
Spermatogenesis in aged mice
The paper reported improved sperm-related outcomes in aged mice alongside effects in Leydig cells. It does not establish human fertility or longevity benefits.
Additional research · Checked 2026-10-12
2Pep-Pedia: FOXO4-DRICommunity source checked
AI-PREPARED SUMMARY
Secondary community overview checked on 12 October 2026. Its practice tables and efficacy claims are not independently validated clinical guidance.
3Baar, M.P., Brandt, R.M., Putavet, D.A., Klein, J.D., Derks, K.W., Bourgeois, B.R., et al. (2017). Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell, 169(1), 132-147.e16.Pep-Pedia report · Primary source not checked
AI-PREPARED SUMMARY
Pep-Pedia reports: Aged mice showed senescent-cell depletion and improvements in kidney, activity and fur measures; selective toxicity was studied under experimental conditions.
Reported population / model
Mouse
Reported study details
5 mg/kg IV · 3 doses every other day · Fast-aging & naturally aged mice
Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.
Read the Pep-Pedia report ↗Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12
4Zhang, L., Sun, J., Wang, B., Ren, J.C., Su, W., Zhang, T. (2020). FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging, 12(2), 1272-1284.Pep-Pedia report · Primary source not checked
AI-PREPARED SUMMARY
Pep-Pedia reports: Aged mice had higher testosterone and steroidogenic enzymes, with lower testicular senescence/inflammatory markers after treatment.
Reported population / model
Mouse
Reported study details
5 mg/kg IP · Every other day × 3 · Aged mice (20-24 months)
Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.
Read the Pep-Pedia report ↗Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12
5Stegen, S., Rinzione, E., Ghubieda, S.M., De Vitto, H., Van den Berghe, G., Lim, K.S. (2021). Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Frontiers in Bioengineering and Biotechnology, 9, 677576.Pep-Pedia report · Primary source not checked
AI-PREPARED SUMMARY
Pep-Pedia reports: More than half of heavily passaged senescent cartilage cells were removed, but surviving cells did not gain cartilage-forming capacity.
Reported population / model
Human cells in vitro
Reported study details
Passaged chondrocytes · Senescence model
Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.
Read the Pep-Pedia report ↗Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12
6Han, L., Zhang, Y., Liu, S., Zhao, Q., et al. (2022). FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway. Journal of Cellular and Molecular Medicine, 26(11), 3269-3281.Pep-Pedia report · Primary source not checked
AI-PREPARED SUMMARY
Pep-Pedia reports: Fibrotic mice had less collagen and senescence-associated signaling; the source compares model effects with pirfenidone, not clinical equivalence.
Reported population / model
Mouse
Reported study details
BLM-induced fibrosis model · Therapeutic administration
Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.
Read the Pep-Pedia report ↗Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12
7Liu, Y., Wang, X., Zhang, H., et al. (2023). FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice. Naunyn-Schmiedeberg's Archives of Pharmacology, 396(7), 1481-1492.Pep-Pedia report · Primary source not checked
AI-PREPARED SUMMARY
Pep-Pedia reports: The pulmonary-fibrosis model showed altered p53 location and lower extracellular-matrix protein accumulation.
Reported population / model
Mouse
Reported study details
Bleomycin model · ECM pathway analysis
Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.
Read the Pep-Pedia report ↗Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12
8Le, H.H., Cinaroglu, S.S., Manber, Z., et al. (2021). Development of a novel senolytic by precise disruption of FOXO4-p53 complex. EBioMedicine, 73, 103641.Linked reference · Not independently reviewed
REFERENCE NOTE
Reference retained from Pep-Pedia’s bibliography. The original source and the website’s description have not been independently verified; the listed title may not match the linked record.
Pep-Pedia bibliography · Checked 2026-10-12
9Baar, M.P., Brandt, R.M., Putavet, D.A., Klein, J.D., Derks, K.W., Bourgeois, B.R., et al. (2017). Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell, 169(1), 132-147.e16.Linked reference · Not independently reviewed
REFERENCE NOTE
Reference retained from Pep-Pedia’s bibliography. The original source and the website’s description have not been independently verified; the listed title may not match the linked record.
Pep-Pedia bibliography · Checked 2026-10-12
10Zhang, L., Sun, J., Wang, B., Ren, J.C., Su, W., Zhang, T. (2020). FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging, 12(2), 1272-1284.Linked reference · Not independently reviewed
REFERENCE NOTE
Reference retained from Pep-Pedia’s bibliography. The original source and the website’s description have not been independently verified; the listed title may not match the linked record.
Pep-Pedia bibliography · Checked 2026-10-12
11Stegen, S., Rinzione, E., Ghubieda, S.M., De Vitto, H., Van den Berghe, G., Lim, K.S. (2021). Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Frontiers in Bioengineering and Biotechnology, 9, 677576.Linked reference · Not independently reviewed
REFERENCE NOTE
Reference retained from Pep-Pedia’s bibliography. The original source and the website’s description have not been independently verified; the listed title may not match the linked record.
Pep-Pedia bibliography · Checked 2026-10-12
12Han, L., Zhang, Y., Liu, S., Zhao, Q., et al. (2022). FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway. Journal of Cellular and Molecular Medicine, 26(11), 3269-3281.Linked reference · Not independently reviewed
REFERENCE NOTE
Reference retained from Pep-Pedia’s bibliography. The original source and the website’s description have not been independently verified; the listed title may not match the linked record.
Pep-Pedia bibliography · Checked 2026-10-12
13Liu, Y., Wang, X., Zhang, H., et al. (2023). FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice. Naunyn-Schmiedeberg's Archives of Pharmacology, 396(7), 1481-1492.Linked reference · Not independently reviewed
REFERENCE NOTE
Reference retained from Pep-Pedia’s bibliography. The original source and the website’s description have not been independently verified; the listed title may not match the linked record.
Pep-Pedia bibliography · Checked 2026-10-12
14Le, H.H., Cinaroglu, S.S., Manber, Z., et al. (2021). Development of a novel senolytic by precise disruption of FOXO4-p53 complex. EBioMedicine, 73, 103641.Linked reference · Not independently reviewed
REFERENCE NOTE
Reference retained from Pep-Pedia’s bibliography. The original source and the website’s description have not been independently verified; the listed title may not match the linked record.
Pep-Pedia bibliography · Checked 2026-10-12
15Pep-Pedia: FOXO4-DRI — reported pharmacokineticsReference estimate; not independently verified human PKCommunity source checked
AI-PREPARED SUMMARY
Lists a half-life of 1 day – 3 days and a peak time of 4 hrs. Stated attribution: Baar et al. 2017 Cell. This value is reported by a secondary reference. The stated attribution has not been independently verified as a route- and formulation-matched human PK measurement. Five half-lives is not complete clearance, and the source’s “cleared” value is not used as a measured endpoint.
Secondary reference page checked; the underlying quantitative claim is not independently confirmed. · Checked 2026-10-12
16Pep-Pedia: FOXO4-DRI — route-specific referenceReference page checked; underlying claims require separate verification.Community source checked
AI-PREPARED SUMMARY
Source page checked across available routes. Protocols, cycles, storage, mechanisms and pairing claims are secondary reports; checking the page does not independently validate those claims. Original concise summaries are used here.
Content coverage audit · Checked 2026-10-12