When Berta Vázquez and her team at the Universitat Autònoma de Barcelona began investigating why men's fertility declines with age, they didn't expect to find answers in a little-studied protein called SIRT7. Yet this overlooked molecular guardian, they discovered, may hold the key to understanding male reproductive aging—and potentially reversing some of its effects.
The finding matters because more people are having children later in life, when sperm quality naturally deteriorates. But the exact molecular machinery behind this decline has remained largely a mystery. Now, research published in Nature Communications reveals that SIRT7 acts as a critical gatekeeper, protecting the genome stability of male germ cells as the years pass. Without it, sperm production falters, DNA damage accumulates, and fertility unravels far faster than it should.
Working with mice, Vázquez's team—collaborating with researchers at the Josep Carreras Leukemia Research Institute in Barcelona and Rutgers University—mapped SIRT7's precise role. The protein is especially active during early stages of germ cell development, particularly in spermatogonia, the stem cells responsible for continuously producing new sperm throughout a man's life. The researchers identified a previously unknown epigenetic mechanism where SIRT7 regulates an epigenetic marker called histone H3K36ac, essentially controlling how tightly DNA is packaged and which genes can be accessed.
When SIRT7 is absent, the consequences are stark: spermatogonia are lost prematurely, DNA damage accumulates during aging or under environmental stress, sperm formation slows with age, and fragmentation of sperm DNA increases. The team also observed that the H3K36ac marker naturally accumulates during testicular aging, suggesting a direct causal link to age-related reproductive decline.
What makes this discovery particularly significant is that SIRT7 belongs to a larger family of proteins already known to combat cellular aging across the body. Most previous research, however, has focused on how these proteins work in female gametes—their role in males has been largely overlooked. "This research shows that SIRT7 is also essential in males, which opens new avenues for understanding male infertility and developing strategies to preserve reproductive health with age," Vázquez explains.
The implications extend beyond natural aging. The findings also point toward ways to protect fertility in cancer patients undergoing chemotherapy, which can damage germ cells. By understanding how SIRT7 shields sperm-producing cells from genomic damage, researchers may develop interventions to safeguard reproductive function in people receiving gonadotoxic treatments.
While this work was conducted in mice, it provides a roadmap for understanding human male reproductive aging at the molecular level. Rather than treating fertility decline as an inevitable consequence of time, the research suggests it stems from specific, potentially modifiable biological mechanisms. For people contemplating parenthood later in life, or those whose fertility has been threatened by medical treatment, this glimpse into the cellular machinery of aging offers genuine hope. The overlooked protein SIRT7 may soon become central to preserving one of life's most fundamental capabilities.