In their experiments, the researchers sought to understand the role of the insulin-like signaling pathway in extending lifespan. This pathway governs growth and metabolic processes in cells throughout the body. The pathway is activated when insulin and insulin-like growth factor-1 switch on proteins inside the cell called insulin receptor substrates (Irs).

Other researchers had shown that reducing the activity of the pathway in roundworms and fruitflies extends lifespan. Despite those tantalizing clues, White said, “The idea that insulin reduces lifespan is difficult to reconcile with decades of clinical practice and scientific investigation to treat diabetes.” “In fact, based on our work on one of the insulin receptor substrates, Irs2, in liver and pancreatic beta cells, we thought more Irs2 would be good for you,” said White. “It reduces the amount of insulin needed in the body to control blood glucose, and it promotes growth, survival and insulin secretion from pancreatic beta cells.
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“Diet, exercise and lower weight keep your peripheral tissues sensitive to insulin. That reduces the amount and duration of insulin secretion needed to keep your glucose under control when you eat. Therefore, the brain is exposed to less insulin. Since insulin turns on Irs2 in the brain, that means lower Irs2 activity, which we’ve linked to longer lifespan in the mouse.”