Exploring the Mechanisms of Testicular Aging: Advances in Biomarker Research.

Aging biomarkers quantify aging progression and provide actionable targets for therapeutic interventions to mitigate age-related decline. This review synthesizes emerging evidence on testicular aging biomarkers, focusing on cellular senescence (Leydig, Sertoli, and endothelial cells), protein homeostasis disruption, mitochondrial dysfunction, germ stem cell depletion, sperm telomere length, epigenetic alterations, oxidative stress, inflammation, and gut microbiota dysbiosis. We propose that testicular aging serves as a critical nexus linking reproductive decline with systemic aging processes, with its pathological progression being quantifiable through specific biomarkers including the Leydig, Sertoli, and endothelial cells, INSL3, ribosomal protein RPL39L, sperm telomere length, relative telomere length mitochondrial translocator protein, and sialic acid. By bridging systemic aging paradigms with testis-specific mechanisms, we emphasize the urgency to identify organ-selective biomarkers for targeted interventions, advancing strategies to preserve male fertility and address population aging challenges.