Graphical Abstract Highlights d A multi-tissue age-related gene expression signature (AGES) is constructed d Linear, early, middle-, and late-life expression changes are discovered d AGES points to potential mechanisms inducing age-related disorders d Gene changes in multiple tissues include upregulation of interferon signaling SUMMARY To understand the changes in gene expression that occur as a result of age, which might create a permissive or causal environment for age-related diseases, we produce a multi-time point age-related gene expression signature (AGES) from liver, kidney, skeletal muscle, and hippocampus of rats, comparing 6-, 9-, 12-, 18-, 21-, 24-, and 27-month-old animals.We focus on genes that changed in one direction throughout the lifespan of the animal, either early in life (early logistic changes), at mid-age (mid-logistic), late in life (late-logistic), or linearly, throughout the lifespan of the animal. The pathways perturbed because of chronological age demonstrate organspecific and more-global effects of aging and point to mechanisms that could potentially be counterregulated pharmacologically to treat age-associated diseases. A small number of genes are regulated by aging in the same manner in every tissue, suggesting they may be more-universal markers of aging.
RESULTSTranscriptional Profiling of Liver, Gastrocnemius Muscle, Kidney, and Hippocampus throughout the Rat Lifespan We sought to establish both tissue-specific and more global aging gene signatures, which could serve as a basis for