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Study · Animal study (in vivo) · mouse · 2020

4 results

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

Zhang C, Xie Y, Chen H, Lv L, Yao J, Zhang M, Xia K, Feng X, Li Y, Liang X, Sun X, Deng C, Liu G

Aging20 Jan 2020Cited by 85 (Europe PMC)

PMID31959736 (opens in a new tab)PMCIDPMC7053614 (opens in a new tab)DOI10.18632/aging.102682 (opens in a new tab)PepBankPUB-31959736
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Summary

Male late-onset hypogonadism is an age-related disease, the core mechanism of which is dysfunction of senescent Leydig cells. Recent studies have shown that elimination of senescent cells can restore proper homeostasis to aging tissue. In the present study, we found that the fork head box O (FOXO) transcription factor FOXO4 was specially expressed in human Leydig cells and that its translocation to the nucleus in the elderly was related to decreased testosterone synthesis. Using hydrogen peroxide-induced senescent TM3 Leydig cells as an in vitro model, we observed that FOXO4 maintains the viability of senescent Leydig cells and suppresses their apoptosis. By disrupting the FOXO4-p53 interaction, FOXO4-DRI, a specific FOXO4 blocker, selectively induced p53 nuclear exclusion and apoptosis in senescent Leydig cells. In naturally aged mice, FOXO4-DRI improved the testicular microenvironment and alleviated age-related testosterone secretion insufficiency. These findings reveal the therapeutic potential of FOXO4-DRI for the treatment of male late-onset hypogonadism.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In naturally aged mice, FOXO4‑DRI improved the testicular microenvironment.

    In plain wordsIn aged mice, FOXO4‑DRI improved conditions inside the testes.

    Peptide
    FOXO4-DRI
    Outcome
    IncreaseTesticular microenvironment
    Study

    mousen: not reported in source

    Naturally aged mice
    Outcome group
    Aging markers · Reproductive and sexual health
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In naturally aged mice, FOXO4-DRI improved the testicular microenvironment and alleviated age-related testosterone secretion insufficiency.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In naturally aged mice, FOXO4‑DRI alleviated age-related testosterone secretion insufficiency.

    In plain wordsIn aged mice, FOXO4‑DRI eased the age-related drop in testosterone release.

    Peptide
    FOXO4-DRI
    Outcome
    IncreaseAge-related testosterone secretion insufficiency
    Study

    mousen: not reported in source

    Naturally aged mice
    Outcome group
    Sex hormones and fertility · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In naturally aged mice, FOXO4-DRI improved the testicular microenvironment and alleviated age-related testosterone secretion insufficiency.
  3. 03LabIn vitro (cells)Mechanism

    In senescent TM3 Leydig cells, FOXO4‑DRI disrupted the FOXO4-p53 interaction and selectively induced p53 nuclear exclusion.

    In plain wordsIn cells, FOXO4‑DRI moved p53 out of the nucleus in aged Leydig cells.

    Peptide
    FOXO4-DRI
    Outcome
    Increasep53 nuclear exclusion in senescent Leydig cells
    Study

    n: not reported in source

    Hydrogen peroxide-induced senescent TM3 Leydig cells
    Outcome group
    Receptor activity and mechanism · Reproductive and sexual health
    Studied dose
    Dose not stated

    Source sentences

    Summary
    By disrupting the FOXO4-p53 interaction, FOXO4-DRI, a specific FOXO4 blocker, selectively induced p53 nuclear exclusion and apoptosis in senescent Leydig cells.
    1 context sentence
    Summary · context
    Using hydrogen peroxide-induced senescent TM3 Leydig cells as an in vitro model, we observed that FOXO4 maintains the viability of senescent Leydig cells and suppresses their apoptosis.
  4. 04LabIn vitro (cells)Mechanism

    In senescent TM3 Leydig cells, FOXO4‑DRI selectively induced apoptosis.

    In plain wordsIn cells, FOXO4‑DRI caused aged Leydig cells to die.

    Peptide
    FOXO4-DRI
    Outcome
    IncreaseApoptosis of senescent Leydig cells
    Study

    n: not reported in source

    Hydrogen peroxide-induced senescent TM3 Leydig cells
    Outcome group
    Cell viability and death · Reproductive and sexual health
    Studied dose
    Dose not stated

    Source sentences

    Summary
    By disrupting the FOXO4-p53 interaction, FOXO4-DRI, a specific FOXO4 blocker, selectively induced p53 nuclear exclusion and apoptosis in senescent Leydig cells.
    1 context sentence
    Summary · context
    Using hydrogen peroxide-induced senescent TM3 Leydig cells as an in vitro model, we observed that FOXO4 maintains the viability of senescent Leydig cells and suppresses their apoptosis.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 21:44 UTC

    Study results updated

  2. Version 1

    13 Oct 2026, 16:31 UTC

    First added · source update from Europe PMC

Subjects

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