While we tend to grow out of monkey business and running in circles as we grow older, exciting new profiles of brain circular RNA (circRNA) dynamics during normal aging have emerged thanks to these two youthful tactics.
This insightful research into non-human primates comes from the groups of Jiali Li (University of the Chinese Academy of Sciences, China) and Yi Zhang (ABLife Inc., China). The talented team utilized circRNA-seq, where linear RNA is digested by RNase R, to deep sequence eight different rhesus macaque (Macaca mulatta) brain regions from two age groups: adult (10 years old) to aged (20 years old). They also validated their results via RT-qPCR analysis.
Here’s what they discovered:
- circRNAs display genome-wide expression in the primate the brain, where 17,050 were identified
- circRNAs map to host genes critical to synaptic signaling and metabolism in the brain
- Clustering of circRNA expression profiles revealed variations influenced by age, brain region, and sex
- 488 circRNAs show brain region specificity
- 468 circRNAs show sex-bias; 274 with a male bias and 194 with a female bias
- 475 circRNAs show age bias; 272 with an old-age bias and 203 with an adult bias
- While the expression of most circRNAs (~80%) doesn’t correlate with linear host mRNAs, a subset primarily correlate positively and this relationship changes during aging
Finally, as brain aging alters the homeostasis of calcium levels critical for synaptic signaling and plasticity, the team focused on two relevant circRNAs. circCACNA2D1 and circCACNA1E derive from voltage-dependent calcium channel genes, where they display increased expression with aging and a negative correlation with linear host mRNA. Overall, these exciting new findings further support the role of circRNAs in the biology of brain aging and offer the first comprehensive non-human primate profiles.
Go run circles around the fountain of youth over at Nature’s Cell Discovery, September 2018.