Triggering of IRE-1 was associated with an inhibition of insulin receptor signaling by the serine phosphorilation of insulin receptor substrate-1 (IRS-1) that usually leads to insulin resistance, which is undoubtedly a marker of adverse prognosis because of its association with multiple comorbidities in aging (Hirosumi et al., 2002). The gene discussed is IRS1; the disease is Insulin resistance.