The massive gene expression changes associated with aging that we detected involved a constellation of biological processes. A gene set annotation analysis revealed that the genes downregulated with increasing BioAge showed significant enrichment for neuronal and synaptic processes, possibly reflecting neuronal depletion or loss of plasticity (Table S3). The upregulated processes include lipid metabolism, FAK signaling and axon guidance as well as the glial marker, GFAP (Table S3). In agreement with an earlier analysis of aging signatures observed in normal brains [2], [3], the upregulated genes contain several oncogenes (TP53, PI3K, PTEN, etc.), shown to be strongly correlated with BioAge in Figure S3.
