TNF and obesity due to melanocortin 4 receptor deficiency: Normal aging has been regarded as a chronic and low-grade pro-inflammatory state, with an over-expression of systemic inflammatory cytokines including IL-1, IL-6 and TNF-α etc. A number of highly prevalent risk factors such as obesity, diabetes, hypertension, and atherosclerosis are increasingly believed to silently contribute to systemic- and neuro-inflammation [44–46].