GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE314nnn/GSE314480/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314480GEOGSEfalseSIRT7 links H3K36ac epigenetic regulation with genome maintenance in the aging mouse testis [ATAC-Seq]Reproductive aging is an increasing health concern affecting family planning and overall well-being. While extensively studied in females, the mechanisms driving male reproductive aging remain largely unexamined. Here we found that mammalian Sirtuin 7 (SIRT7) sustains spermatogenesis in an age-dependent manner through the control of histone 3 lysine 36 acetylation (H3K36ac). SIRT7 deficiency in mice resulted in increased levels of H3K36ac in spermatogonia and spermatocytes, a pattern also observed during natural testicular aging. SIRT7 deficiency altered chromatin accessibility, which was directly linked to H3K36ac activity in a germ cell line, and increased vulnerability to genotoxic stress. Importantly, undifferentiated spermatogonia, which are required for continuous sperm production, decreased prematurely in Sirt7-/- mice and showed enhanced genome damage accumulation during aging or under acute environmental stress. These changes were concurrent with age-dependent defects in double strand break (DBS) repair and partial meiotic arrest. Taken together, our results indicate that SIRT7 connects H3K36ac epigenetic regulation to long-term genome stability in male germ cells, ensuring steady-state spermatogenesis during the lengthy male reproductive lifespan.2026/03/31GSE314480GSM9396964GSM9396963GSM9396962GSM9396961GSM9396960GSM939695928457314480Mus musculus