The sex-specific metabolic signature of C57BL/6NRj mice during aging

Due to intact reactive oxygen species homeostasis and glucose metabolism, C57BL/6NRj mice are especially suitable to study cellular alterations in metabolism. We applied Nuclear Magnetic resonance spectroscopy to analyze five different tissues of this mouse strain during aging and included female and male mice aged 3, 6, 12, and 24 months. Metabolite signatures allowed separation between the age groups in all tissues, and we identified the most prominently changing metabolites in female and male tissues. A refined analysis of individual metabolite levels during aging revealed an early onset of age-related changes at 6 months, sex-specific differences in the liver, and a biphasic pattern for various metabolites in the brain, heart, liver, and lung. In contrast, a linear decrease of amino acids was apparent in muscle tissues. Based on these results, we assume that age-related metabolic alterations happen at a comparably early aging state and are potentially associated with a metabolic switch. Moreover, identified differences between female and male tissues stress the importance of distinguishing between sexes when studying age-related changes and developing new treatment approaches. Besides, metabolomic features seem to be highly dependent on the genetic background of mouse strains.