Age-related erectile dysfunction (ARED) represents a significant clinical challenge due to the interplay between chronic comorbidities and age-related physiological decline. This study investigated the therapeutic potential of near-infrared photobiomodulation therapy (NIR-PBMT) in ARED mice, focusing on molecular and physiological mechanisms of complex erectile function restoration. Aged mice received NIR-PBMT (4 J cm−2) every 48 h for 2 weeks. Erectile function was evaluated using the maximum intracavernosal pressure/mean arterial pressure (ICPmax/MAP) ratio following cavernous nerve stimulation. Histological analysis and western blotting revealed significant improvements in penile tissue architecture, including increased smooth muscle content, reduced collagen deposition, and altered expression of senescence markers (p21 and phosphorylated H2A histone family member X [γ-H2A.X]) and endothelial nitric oxide synthase (eNOS). In vitro studies using human corpus cavernous endothelial cells (HCCECs) demonstrated that NIR-PBMT reduced cellular senescence (assessed via SA-β-galactosidase staining), enhanced nitric oxide (NO) production, and improved mitochondrial network integrity. Angiogenesis assays further confirmed the pro-angiogenic effects of NIR-PBMT. Collectively, these findings highlight NIR-PBMT as a promising non-invasive therapy for ARED, acting through multiple pathways to reverse pathological remodeling and restore endothelial function. Future translational research is necessary to validate its clinical efficacy and optimize treatment protocols.

Keywords: age-related erectile dysfunction; angiogenesis; cellular senescence; mitochondria; near-infrared photobiomodulation
therapy

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