SIRT7 links H3K36ac epigenetic regulation with genome maintenance in the aging mouse testis

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.