Testicular ageing as a central hallmark of male senescence: characteristics, molecular mechanisms and emerging therapeutic strategies

BACKGROUND: The testis is a male-specific organ that plays a central role in spermatogenesis and androgen secretion. Testicular ageing is a hallmark of male senescence. However, the underlying mechanisms, as well as strategies to prevent, delay, or reverse this process, remain incompletely understood. DISCUSSION: As a critical component of male ageing, testicular ageing has attracted broad scientific attention, with ongoing efforts to identify effective strategies to delay or prevent its onset, though therapeutic efficacy remains limited. In this review, we summarise the biological and clinical features of testicular ageing, discuss its underlying molecular and cellular mechanisms, and highlight emerging strategies aimed at mitigating age-related testicular dysfunction, with the goal of advancing understanding and improving therapeutic outcomes. CONCLUSIONS: Testicular ageing is a defining feature of male senescence, marked by progressive structural deterioration and declining steroidogenic and spermatogenic capacity. Although lifestyle, pharmacological, and stem-cell-based interventions show promise, their clinical applicability remains limited. A deeper mechanistic understanding and well-designed, large-scale prospective studies are essential to establish effective strategies for delaying or preventing testicular ageing.