In simulated sepsis conditions, the silent information regulator-1 (SIRT-1)-activator-3 (a selective synthetic agonist of SIRT-1) activation of the peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1α) and nuclear factor erythroid 2-like 2 (NFE2L2) pathways demonstrated a protective effect on cells against LPS/PepG-induced loss of mitochondrial membrane potential and metabolic activity, as well as a reduction in interleukin-6 (IL-6) responses. The gene discussed is NFE2L2; the disease is Sepsis.