A cross-species multi-omics analyze uncovers conserved molecular mechanisms underlying age-related erectile dysfunction.

BACKGROUND: The urgent need for new treatments is driven by the challenging clinical situation of age-related erectile dysfunction (ARED). AIM: To clarify the conserved molecular mechanisms of ARED across species using multi-omics. METHODS: Rat and mouse models with ARED were developed to facilitate the extraction of mRNA and proteins from the corpus cavernosum for high-throughput sequencing. Bioinformatics techniques were employed to analyze differentially expressed genes and to conduct analyses using the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and protein-protein interaction networks. Verification of the results was carried out using immunofluorescence, hematoxylin-eosin staining, and Masson staining. OUTCOMES: The multi-omics profiles of ARED rats and mice were analyzed and validated across species. RESULTS: In both species, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses of transcriptomic and proteomic data revealed that differentially expressed genes were predominantly enriched in pathways associated with alterations in extracellular matrix composition, downregulation of mitochondrial activity, and disruption of protein homeostasis. Immunofluorescence analysis demonstrated an upregulation of reactive oxygen species expression, coupled with a downregulation of Aldh18a1, collagen, and collagen I expression in the corpus cavernosum of mice and rats with ARED. CLINICAL IMPLICATIONS: To offer a novel approach for enhancing the erectile function in patients with ARED. STRENGTHS AND LIMITATIONS: The primary strength of this study lies in its utilization of cross-species multi-omics sequencing, which has elucidated the conserved molecular mechanisms underlying ARED. However, a significant limitation is the absence of subsequent validation in patients with ARED. CONCLUSIONS: Cross-species multi-omics comparisons present a potentially innovative approach for elucidating the underlying mechanisms and identifying preventive and therapeutic targets for ARED.