FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells.
Li. Yanqing Y; Zhang. Chi C; Cheng. Haicheng H; Lv. LinYan L; Zhu. Xinning X; Ma. Menghui M; Xu. Zhenhan Z; He. Junxian J; Xie. Yun Y; Yang. Xing X; Liang. Xiaoyan X; Deng. Chunhua C; Liu. Guihua G
Key Findings
- FOXO4-DRI blocks the FOXO4‑p53 interaction, triggering apoptosis specifically in senescent Leydig cells.
- Removal of senescent Leydig cells reduces secretion of senescence‑associated secretory phenotype (SASP) factors and boosts growth of spermatogenic GC‑1 SPG cells in co‑culture.
- Aged mice given FOXO4‑DRI showed improved sperm quality and enhanced spermatogenesis compared with untreated controls.
Practical Outcomes
- The peptide shows potential for reversing age‑related declines in male fertility, but it has only been tested in mice so far. No human dosage, safety, or delivery method is known, making it premature for self‑experimentation. Enthusiasts should view this as an early‑stage discovery that may inform future anti‑aging protocols once more data become available.
Summary
A study in old mice found that a short peptide called FOXO4-DRI can kill aging Leydig cells in the testicles, lower the harmful chemicals they release, and help sperm production improve. Treated mice had better sperm quality and more active spermatogenesis, suggesting the peptide might counter age‑related male fertility loss, but the work is still limited to animal experiments.
Abstract
Male ageing is always accompanied by decreased fertility. The forkhead O (FOXO) transcription factor FOXO4 is reported to be highly expressed in senescent cells. Upon activation, it binds p53 in the nucleus, preventing senescent cell apoptosis and maintaining senescent cells in situ. Leydig cells play key roles in assisting spermatogenesis. Leydig cell senescence leads to deterioration of the microenvironment of the testes and impairs spermatogenesis. In this study, we observed that FOXO4-DRI, a specific FOXO4- p53 binding blocker, induced apoptosis in senescent Leydig cells, reduced the secretion of certain Senescence-Associated Secretory Phenotype and improved the proliferation of cocultured GC-1 SPG cells. In naturally aged mice, FOXO4-DRI-treated aged mice exhibited increased sperm quality and improved spermatogenesis.
Study Information
pubmed
2024
2024-07-19T00:00:00.000Z
10.1016/j.exger.2024.112522
6
37