(A) Experimental design includes comparing gene expression (RNA-Seq) from livers of young (3 months), middle-aged (12 months), and old (21 months) and nucleosome occupancy (MNase-Seq) of young and old livers. (B) RNA-Seq track view in Integrative Genome Viewer (IGV) of expression of Cidea, a target of nuclear receptors Pparα and Pparγ, not expressed in young healthy livers and highly induced in steatotic older hepatocytes. (C) Heat map of differentially expressed genes in aged livers (FDR 5%, 727 upregulated and 525 downregulated). (D) Regulators of gene expression in heat map in (C). Factors regulating lipid synthesis and storage are nuclear receptors Pparα (p-value 1.1×10−20), Pparγ (p-value 2.7×10−8), and LXRα (p-value 4.2×10−13), and Cebpb (p-value 2.1×10−9). Additional regulators include Nf-κb (p-value 1.8×10−3), PI3K (p-value 6.4×10−6), and Xbp1 (p-value 3.6×10−4). Networks with upregulated and downregulated targets are shown in red and blue, respectively. P values determined by Fisher’s exact test (using Ingenuity Pathway Analysis).