We also noticed that the genes upregulated with age in normal samples could be further dissected using a metagene discovery approach (see Methods). We focused on the normal samples with relatively low BioAge (BioAge<0) and found a large metagene with exceptionally high mutual correlation between the genes. We named this metagene Lipa because it included APOE, PPARA, γ-protocadherins, and other genes involved in lipid metabolism, amino acid metabolism and cell adhesion. Other notable Lipa genes included HES1, TGFB2, NTRK2, and WIF1. This metagene was much more coherent in normal samples than in AD samples. The corresponding Lipa biomarker indicated an average 3-fold upregulation of these genes early in the aging process. Figure S4 further illustrates the relationships between metagene-based biomarkers and selected component genes mentioned in the text.
