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Senescent Leydig Cell Elimination & Testosterone Restoration in Aged Mice (Aging / PMC, 2020) FOXO4-DRI Disrupts FOXO4-p53 in Senescent Leydig Cells and Improves Testicular Microenvironment A study published in Aging (and indexed on PMC) demonstrated that FOXO4 is specifically expressed in human Leydig cells, with nuclear translocation of FOXO4 in elderly men correlating with decreased testosterone synthesis

However, the most worrying are the long-term adverse effects that have been described, such as an increase in cardiovascular complications, the development of T2D, and different types of cancer, which is why its application in real life as an antiaging therapy continues to be controversial and requires further studies to define the stage in life in which it would be most useful, the optimal time of use, and ways of monitoring and preventing its adverse effects

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