IRS1 and Insulin resistance: While the effect of insulin sensitivity on lifespan is complex – some insulin-resistant mice, such as mice lacking IRS1, are long lived (Taguchi et al., 2007; Selman et al., 2008, 2011) – many long-lived mouse models have increased insulin sensitivity, and diet-induced insulin resistance shortens mammalian lifespan (Kenyon, 2001).