Mus musculus Raw sequence reads. Mus musculus

Testicular aging commonly results in testosterone deficiency and impaired spermatogenesis, yet the underlying mechanisms remain poorly understood. In this study, we discovered that the expression of Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthetase 2), the gene encoding the rate-limiting enzyme in ketogenesis, was significantly reduced in Leydig cells (LCs) from aged mice. We treated the mouse LC cell line MLTC-1 with DMSO or the HMGCS2 inhibitor Hymeglusin and observed transcriptomic changes similar to those seen in natural aging, confirming the pivotal role of Hmgcs2 in driving LC senescence and testicular aging.