ИСТИНА

Dozens of pharmacological, genetic and dietary interventions leading to lifespan extension are known for a variety of organisms ranging from yeasts to mammals. Although some key molecular players behind lifespan extension have been uncovered, common mechanisms of different interventions remain unclear. Here we fill this gap by performing systemic analyses of gene expression across longevity interventions in mouse using our RNA-seq data and integrating publicly available data into a single study. By carrying hepatic RNA-seq across 8 longevity interventions in mice, we showed that interventions tend to regulate some common pathways and feminize males through upregulation of xenobiotic metabolism and downregulation of complement and coagulation cascades. We then aggregated all publicly available data and expanded the analysis to 17 interventions. We identified persistent common gene expression signatures across lifespan-extending interventions, including upregulation of genes associated with glucose and amino acid metabolism, ribosome proteins and xenobiotic metabolizing enzymes regulated by NRF2. We further found that genes related to oxidative phosphorylation and hepatic regulation of immune response could serve as both qualitative and quantitative predictors of lifespan extension. Many dietary and genetic interventions exhibited similar transcriptome changes, whereas rapamycin and some other conditions consistently showed distinct patterns, suggesting both common and intervention-specific mechanisms that promote longevity. Finally, we showed that the identified gene expression signatures could be used for the identification of new lifespan-extending interventions. Our work investigated gene expression of nearly all known lifespan-extending interventions. We characterized common and lifespan associated signatures and applied them for the identification of new interventions. These findings provide insights into the mechanisms of lifespan extension in mammals.