Fig. 4. Cellular allostatic load involves transcriptional upregulation of OxPhos and mitochondrial biogenesis.

(A) Heatmaps showing the effect of Dex treatment on the expression of glycolytic genes, expressed as the Log₂ of fold change (Log₂FC) of normalized gene expression relative to the corresponding control time points for each donor. (B) Same as A but for genes encoding the subunits of complexes I, II, III, IV and V of the OxPhos system, with mitochondrial-encoded genes marked with ❖ (C-E). Same as A and B but for genes encoding proteins associated with (C) mtDNA maintenance, (D) mtDNA replication, and (E) mitochondrial biogenesis. Two key regulators of mitochondrial biogenesis, one positive (PGC-1a) and one negative (NRIP1) are highlighted, showing expression signatures consistent with both activated and un-repressed mitochondrial biogenesis. (F) Average effect of Dex treatment shown in A-E. Each datapoint represents the gene average of the Log₂FC values throughout the entire lifespan of the three donors (n = 28 timepoints). Average graphs are mean ± SEM, with each gene shown as a single datapoint. One-sample t-test different than 0, * p < 0.05, * * p < 0.01, * ** p < 0.001, * ** * p < 0.0001, ns: not significant. n = 3 donors per group, 9–10 timepoints per donor. Heatmap row annotation with individual gene names is provided in Supplementary Material Fig. S4.