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Protocols · Longevity

FOXO4-DRI dosage protocol

Dosage and protocol information sourced exclusively from PeptideDosages.com.

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Dosage and protocol figures on this page are reproduced only from the matching PeptideDosages.com protocol. The 3 ml table is arithmetic based on those source amounts and the listed vial sizes. Educational research only — not instructions or medical advice.

Dosage chart

The dosage amounts and schedules below come only from PeptideDosages.com. Syringe-unit figures are mathematical conversions of those source amounts using exactly 3 ml of bacteriostatic water. Educational reference only — not instructions or medical advice.

FOXO4-DRI · 10 mg Vial

FOXO4-DRI is dosed at 250 mcg–500 mcg daily via subcutaneous injection in educational protocols.

Typical daily range
250–500 mcg once daily (gradual titration over 16 weeks).

Standard / Gradual Approach

WeekDaily Dose (mcg)
Weeks 1–4250 mcg
Weeks 5–8375 mcg
Weeks 9–12500 mcg
Weeks 13–16500 mcg

3 ml conversion

10 mg + 3 ml = 3.33 mg/ml. Choose your vial strength to update the units below.

Source doseU-100 syringe
250 mcg7.5 units
375 mcg11 units
500 mcg15 units
Source chart on peptidedosages.com

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FOXO4-DRI: research background

What FOXO4-DRI Is

FOXO4-DRI (FOXO4-D-Retro-Inverso) is a synthetic peptide that functions as a senolytic compound, meaning it can selectively eliminate senescent cells (PMID 40593617, PMID 41625068). It is described as a cell-permeable peptide that specifically targets the interaction between FOXO4 and p53 (PMID 36515093, PMID 41625068).

How FOXO4-DRI Is Thought to Work

FOXO4-DRI is designed to disrupt the interaction between the FOXO4 protein and the p53 tumor suppressor protein, an interaction critical for the survival of senescent cells (PMID 40593617, PMID 31959736, PMID 41625068). Normally, FOXO4 binds to p53 in the nucleus, preventing senescent cell apoptosis (programmed cell death) (PMID 39025385, PMID 31959736). FOXO4-DRI binds to the disordered p53 transactivation domain, forming a transiently folded complex, with both the FOXO4-derived region and a cationic cell permeability peptide contributing to this interaction (PMID 40593617). This disruption leads to p53 nuclear exclusion and subsequent activation of the p53/BCL-2/Caspase-3 signaling pathway, which induces selective apoptosis in senescent cells (PMID 41625068, PMID 39994346, PMID 31959736, PMID 39025385, PMID 37074394). P53 phosphorylation enhances the affinity for FOXO4 and FOXO4-DRI (PMID 40593617).

Laboratory and Animal Studies Report

In cell studies, FOXO4-DRI induced apoptosis in senescent Leydig cells (cells in the testes) (PMID 31959736, PMID 39025385), senescent keloid fibroblasts (cells in scar tissue) (PMID 39994346), and senescent human chondrocytes (cartilage cells) (PMID 33996787). It also alleviated endothelial cell senescence (cells lining blood vessels) (PMID 41625068) and reduced the secretion of senescence-associated secretory phenotype (SASP) components from Leydig cells (PMID 39025385). In animal models, FOXO4-DRI injection in naturally aged and induced aging mice suppressed aortic aging and improved aortic function (PMID 41625068). It also improved spermatogenesis and sperm quality in aged mice by reducing SASP secretion from Leydig cells (PMID 39025385) and alleviated age-related testosterone secretion insufficiency (PMID 31959736). In a bleomycin-induced pulmonary fibrosis mouse model, FOXO4-DRI administration led to milder pathological changes and less collagen deposition, resetting intranuclear p53 distribution and decreasing total extracellular matrix proteins (PMID 37074394). However, in studies of pulmonary hypertension, FOXO4-DRI eliminated senescent pulmonary endothelial cells, which was associated with worsened pulmonary hypertension outcomes in mice and rats (PMID 36515093).

Open Questions and Limitations

While FOXO4-DRI can remove senescent cells in expanded human chondrocytes, its utility in promoting cartilage formation from these cells requires further investigation (PMID 33996787). The elimination of senescent cells by senolytics like FOXO4-DRI may worsen conditions in specific contexts, such as pulmonary hypertension (PMID 36515093).

Studies cited in this section

Summarised from the PubMed abstracts listed above. Educational reference only — not medical advice or instructions.

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