FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice
Chi Zhang, Yun Xie, Haicheng Chen, Linyan Lv, Jiahui Yao, Min Zhang, Kai Xia, Xin Feng, Yanqing Li, Xiaoyan Liang, Xiangzhou Sun, Chunhua Deng, Guihua Liu
Abstract
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.
Topics & Concepts
Leydig cellInternal medicineEndocrinologyApoptosisTestosterone (patch)BiologySecretionCancer researchCell biologyMedicineBiochemistryHormoneLuteinizing hormoneFOXO transcription factor regulationGenetics, Aging, and Longevity in Model OrganismsSperm and Testicular Function