INS and Hypoinsulinemia: Arum et al. demonstrated that mice deficient in growth hormone receptor (GHR)/binding protein gene display hypoinsulinemia, higher sensitivity to insulin and prolonged lifespan even though they are smaller in size [55], while insertion of Igf1 gene under the control of a rat insulin promoter (RIP) can reverse the above phenotypes, supporting that IGF1R is a new aging marker [28, 55].