摘要:SummaryLifespan is limited both by intrinsic decline in vigor with age and by accumulation of external insults. There exists a general picture of the deficits of aging, one that is reflected in a pattern of age-correlated changes in gene expression conserved across species. Here, however, by comparing gene expression profiling ofDrosophilaraised either conventionally, or free of bacteria, we show that ∼70% of these conserved, age-associated changes in gene expression fail to occur in germ-free flies. Among the processes that fail to show time-dependent change under germ-free conditions are two aging features that are observed across phylogeny, declining expression of stress response genes and increasing expression of innate immune genes. These comprise adaptive strategies the organism uses to respond to bacteria, rather than being inevitable components of age-dependent decline. Changes in other processes are independent of the microbiome and can serve as autonomous markers of aging of the individual.Graphical abstractDisplay OmittedHighlights•70% of the changes in gene expression during aging are responses to the microbiome•Some of the most common features of aging never occur in flies that are germ-free•Stress response, immunity, and most metabolic changes are microbiome-dependent•Microbiome-independent features of aging can serve as biomarkers of ageBiological sciences; physiology; microbiology; microbiome