To highlight this idea of a balanced activation of pathways such as SIRT1 or AMPK, Palomera et al. [142] showed that aged mice (24 month) did not respond to 160 mg/kg RSV following an inflammatory lipopolysaccharide challenge (saw no reductions in TLR4, IL-6, or TNF-α), lending credence to the idea that mismanagement of cellular stressors will impair the cellular ability to deal with metabolic stressors such as T2D, obesity, or neuroinflammation. The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.