Rishik, S.; Nutma, E.; Ludwig, N.; Fischer, U.; Tänzer, T.; Rheinheimer, S.; Hart, M.; Gröger, L.; Meerjanssen, J.; Flotho, M.; Esteban, M. A.; Middeldorp, J.; Keller, A.

Despite macaque's centrality in research, no macaque miRNA aging atlas exists. Thus, we sequenced small RNA from 11 organs, with a special focus on brain by including 24 brain regions, sampling males and females between ages 3-35 years. Heart, adrenal gland, corpus callosum and caudate putamen showed the most age-deregulated miRNA trajectories. The MIR-154 family, located inside the imprinted, rejuvenation-associated Dlk-Dio3 cluster was particularly vulnerable. Known age-associated miRNA families LET-7, MIR-29, MIR-17 and MIR-92 were strongly deregulated, with heavy dependence on tissue and sex. MiRNA genomic clusters deregulation was concordant within tissue-sex combinations, implicating upstream regulation rather than random noise. Cross-species comparison with mouse showed ancient miRNAs dominating age-deregulated trajectories. Deregulation direction in tissues-sex was conserved between species at the family/cluster levels, but conservation substantially weakened at individual miRNA level. Thus, our study marks a decisive step in translating miRNA aging trajectories between two of the most popular model organisms.