Research Perspective Volume 3, Issue 3 pp 325—328

Figure 2. Proposed model by which hypothalamic SIRT1 may control lifespan. Hypothalamic neurons control insulin sensitivity in liver and skeletal muscle and the content/activity of brown adipose tissue (BAT) in visceral fat. Recently, we have shown that SIRT1 in hypothalamic POMC neurons governs BAT in perigonadal fat. The model depicted herein predicts that hypothalamic SIRT1 regulates aspects of the metabolic aging process in peripheral organs (e.g.: insulin sensitivity in liver and skeletal muscle and BAT content/activity in fat depots) and by doing so influences the amounts of circulating adipo-, hepato-, and myo-kines which ultimately contribute to changes in organismal lifespan. Experiments aimed at directly testing whether SIRT1 in hypothalamic neurons controls hepatic and/or skeletal muscle insulin sensitivity, and/or exerts any effects on longevity are warranted.