When we checked for insulin signaling in the aged liver by immunoblotting (Figure 5C), we noticed the levels of total INSRB protein was reduced (Figure 5D; p=0.0220), which might be due to chronic exposure to hyperinsulinemia (Ronnett et al., 1982; Palsgaard et al., 2009) that can, in part, lead to insulin resistance. The gene discussed is INS; the disease is hyperinsulinism.