Mappinig the foci of rejuvenation interventions across the mouse central nervous system

Dietary, genetic and pharmacological interventions can extend health- and lifespan in diverse model organisms whilst delaying the onset of age-related pathologies. In the context of the brain, several of these interventions have shown to improve molecular, structural and cognitive hallmarks of brain aging. However, there is limited quantitative knowledge on where in the brain these interventions are most active and to what degree their molecular mechanisms overlap. Here we performed region-resolved RNA-seq of the brain of aged mice either subjected to acute dietary restriction (aDR), injection of young mouse plasma (YMP), as well as their corresponding controls (ad libitium feeding and PBS injection, respectively). This encompasses 229 samples dissected from 15 regions. We reveal that each rejuvenation intervention impacts gene expression in a region-dependent manner, varying in timing, magnitude and biological function. mRNA-seq data of 15 distinct brain regions sampled from 19-months-old C57BL/6JN mice) were generated by deep sequencing using Illumina sequencing. One group of mice (Young Plasma Injection group) received retro-orbital injections of either Young Mouse Plasma (YMP) or PBS (n = 3-4 males per treatment). The second group (Dietary intervention group) of mice was either dietary restricted (aDR) or received ad libitum (AL) feeding (n = 4-5 females per diet). mRNA-seq of liver tissue of all mice in the Dietary Intervention group was additionally generated to assess efficacy of dietary restriction protocol.