GSE121330
Transcriptomic profiling reveals distinct modes of aging in the kidney
The kidney is an excellent model for studying organ aging, but little is known about the molecular changes that take place during the aging process. In this article we measured mRNA expression and protein expression in a large cohort of Diversity Outbred mice at 6, 12, and 18 months of age, and studied the relationship between the changes we observe in mRNA and protein expression as a function of age. We observed enrichments of specific pathways including those that were previously observed to have significant changes with age at the mRNA level, and here we also identified enriched pathways at the protein level. Our analysis of the direction of change in mRNA and protein levels with age at the total population level revealed distinct functional groups that have either concordant or discordant changes in expression levels. The age-interactive quantitative trait loci (QTL) analysis of mRNA (eQTL) and protein (pQTL) revealed many distantly regulated loci as opposed to the many locally regulated eQTL and pQTL observed without age-interaction. From this, we found a locus on chromosome 12 and chromosome 15 to regulate many age-interactive eQTL and pQTL respectively. Overall, our findings demonstrate that the changes with age in the kidney at the protein level are distinctly different from the changes at the mRNA level and are not mediated by mRNA expression. Overall design: Kidneys of 188 Diversity Outbred mice at 6-months, 12-months, and 18-months of age were sequenced using 100bp single-end HiSeq 2500 to understand transcriptional changes that occur in the aging kidney.