Temporal multi-omics reveals coordinated remodeling of the gut microbial-metabolic environment and testicular mitochondrial programs in aging mice

Here, we profiled male mice at 5, 10, 15 and 20 months using testicular transcriptomics, total and mitochondrial-enriched proteomics, gut 16S rRNA gene sequencing, untargeted gut metabolomics and immune-factor profiling.

Across molecular layers, the most pronounced remodeling occurred during late life, particularly between 15 and 20 months, with coordinated attenuation of meiotic, spermiogenic, mitochondrial-translation and respiratory-chain programs. In parallel, senescence-associated, macrophage-associated and inflammatory signals increased within the testicular niche. Mitochondrial-enriched proteomics further uncovered compartment-selective changes that were not consistently reflected at the RNA or total-proteome level.