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Fx41.8

FOXO4-DRI Research

Mostly mechanism / observationalLimited safety

5 peer-reviewed studies

What the evidence says

Mostly mechanism / observational

Most FOXO4-DRI studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.

Most evidence is from mixed-quality studies published 2017–2025.

Based on 5 studies

Confidence

Low

By outcome

Senescence & aging (preclinical)
Mostly mechanism / observational5 studies
Tumor microenvironment
Mostly mechanism / observational3 studies

Active research area

3 studies in the last 5 years

20172025

1Animal2017

Targeted apoptosis of senescent cells by a FOXO4 peptide restored tissue homeostasis in response to chemotoxicity and aging.

Baar, Brandt, Putavet, Klein, Derks, Bourgeois · Cell (2017)

Landmark 2017 Cell study introducing FOXO4-DRI as a senolytic peptide
Selectively cleared senescent cells in aged and chemotherapy-treated mice
Restored fitness, fur density, and renal function

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2Animal2020

FOXO4-DRI alleviated age-related testosterone insufficiency by targeting senescent Leydig cells.

Zhang, Xie, Chen, Lv, Yao, Zhang · Aging (2020)

Animal study applying FOXO4-DRI to senescent testicular Leydig cells
Improved testosterone secretion by clearing senescent cells
Extends the senolytic concept to reproductive aging

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3In Vitro2021

The senolytic peptide FOXO4-DRI selectively removed senescent cells from in-vitro expanded human chondrocytes.

Huang, He, Makarcyzk, Lin · Frontiers in bioengineering and biotechnology (2021)

Cell study using FOXO4-DRI to clear senescent cells from expanded human chondrocytes
Relevant to autologous chondrocyte implantation quality
Demonstrates senolysis in a human-cell culture system

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4In Vitro2021

Targeting senescence-like fibroblasts radiosensitized non-small-cell lung cancer in preclinical models.

Meng, Li, Wan, Sun, Dai, Huang · JCI insight (2021)

Preclinical study targeting senescent fibroblasts in the tumor microenvironment
Senolytic approach altered radiotherapy response in NSCLC models
Illustrates both potential benefit and tumor-context complexity

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5In Vitro2025

FOXO4-DRI induced apoptosis of senescent keloid fibroblasts.

Kong, Li, Liu, Pan, Fu, Xiao · Communications biology (2025)

Recent study applying FOXO4-DRI to senescent keloid fibroblasts
Promoted apoptosis via nuclear exclusion of target factors
Broadens the catalog of senolytic applications

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View in Research Library

FOXO4-DRI Research

Mostly mechanism / observational

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.

FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.

Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes.

Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis.

FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation.