Project description:The red sea urchin, Mesocentrotus franciscanus, is one the earth’s longest-lived animals, reported to live more than 100 years with indeterminate growth, life-long reproduction and no increase in mortality rate with age. To explore the idea that transcriptional stability is a key determinant of longevity and negligible senescence, age-related gene expression was examined in three tissues of the red sea urchin (Aristotle’s lantern muscle, esophagus and radial nerve cord). Genome-wide transcriptional profiling using RNA-Seq revealed remarkable stability in muscle and esophagus with very few age-related changes in gene expression. In contrast, expression of more than 900 genes was significantly altered with age in radial nerve cord including genes involved in nerve function, signaling, metabolism, cytoskeleton, transcriptional regulation and chromatin modification. Notably, there was an upregulation in expression of genes involved in synaptogenesis and axonogenesis suggesting enhanced nervous system activity with age. Among the signaling pathways affected by age, there was a downregulation in expression of key components of the mTOR signaling pathway and an upregulation of negative regulators of this pathway. This was accompanied by a reduction in expression of genes involved in protein synthesis and mitochondrial function and an increase in expression of genes that promote autophagy. Downregulation of the mTOR pathway together with the other observed changes reveals a unique age-related gene expression profile in the red sea urchin nervous system that may contribute to mitigation of the detrimental effects of aging in this long-lived animal.