Gonad Rejuvenation as a Therapeutic Strategy for Extending Human Healthspan and Lifespan: Mechanistic Insights and Future Perspectives
Panayiotis Michael Zavos, Carmen Navarro.
The progressive decline of gonadal function is a hallmark of human aging, characterized by reduced sex steroid production, impaired gametogenesis, and diminished endocrine signaling. This decline is associated with multiple systemic consequences, including loss of muscle mass, decreased bone density, metabolic dysregulation, cognitive decline, and increased susceptibility to chronic disease. Emerging research suggests that rejuvenating gonadal function could restore youthful endocrine profiles, influence hallmark pathways of aging, and potentially extend both healthspan and lifespan. This article reviews the physiological role of the gonads across the human lifespan, the systemic consequences of gonadal aging, and the potential for gonadal rejuvenation therapies to mitigate age-related decline. We also present a theoretical framework for the mechanisms by which gonad restoration may influence longevity, supported by evidence from endocrinology, geroscience, and reproductive biology. Finally, we discuss the challenges, ethical considerations, and future research directions necessary to advance this field toward clinical application.
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