Genes upregulated with BioAge point to activation of cell cycle regulation pathways, lipid metabolism and axon guidance pathways (Table S3). Misexpression of cell cycle genes in post-mitotic neurons has been observed in aging and in AD and is postulated to be an important mechanism of neurodegeneration [37], [38]. The enrichment for oncogenes within this set is consistent with biological responses to genotoxic stress activated during aging in an increasingly larger population of brain cells. Genes downregulated with BioAge were associated with a decrease in neuronal activity. Most of these genes maintained a strong correlation (connectivity) with BioAge throughout the entire range of the biomarker. This implies that the core of biological aging is one gradual change rather than several distinct transitions.
