Figure 5. Regional rate of decreased AG correlates with regional metabolic and transcriptional neoteny.

(A) AG was calculated for each region using the combined literature-based whole brain and local-to-global values (see Methods). Change in AG per year was then calculated for each region and compared to the AG in that region in young adults aged 20 – 23 years. Regions with the highest AG in young adults showed the most rapid loss of AG per year (Pearson’s r = −0.87, p < 3×10⁻¹⁴), including such regions as the medial frontal cortex and the precuneus. (B) The BrainSpan lifespan human brain transcriptional data was used to calculate a regional neoteny index, which is a measure of the persistence of developmentally related gene expression (Goyal et al., 2014), for each of the 15 regions assessed by the BrainSpan data set as compared to the cerebellum. In addition to the cerebellum, the 15 regions include dorsolateral prefrontal cortex; ventrolateral, medial and orbital frontal cortex; primary motor, somatosensory, auditory and visual cortex; posterior inferior parietal cortex; posterior superior and inferior temporal cortex; hippocampus and amygdala; striatum; and thalamus (Kang et al., 2011). The loss of AG per year for these 15 regions inversely correlates with their regional neoteny index (Pearson’s r = −0.79, 95% CI −0.47 to −0.93, p < 0.0005). These results suggest that the largest aging-related change in AG occurs in the most metabolic and transcriptionally neotenous regions of the human brain, accounting for the flattening of AG seen in Figure 4.