Recent findings demonstrate that nutrition during the fetal and neonatal periods can affect lifespan of an organism. Our previous studies in rodents using a maternal low protein diet, have shown that limiting protein and growth during lactation [postnatal low protein (PLP group)] increases longevity, while in utero growth restriction (IUGR) followed by 'catch up growth' [recuperated group] shortens lifespan. The aim of this study was to investigate mechanisms in early postnatal life that could underlie these substantial differences in longevity. At weaning PLP animals had improved insulin sensitivity as suggested by lower concentrations of insulin required to maintain concentrations of glucose similar to these of the control group, and significant upregulation of IR, IGF1-R, Akt1, Akt2 and Akt phosphorylated at Ser 473 in the kidney. These animals also had significantly increased SIRT1 expression. Expression of the anti-oxidant enzymes catalase, CuZnSOD and GPx-1 was elevated in these animals. In contrast, recuperated animals had a significantly increased fasting glucose concentration, while insulin levels remained comparable to those of the control group suggesting relative insulin resistance. MnSOD expression was increased in these animals. This data suggests that early nutrition can lead to alterations in insulin sensitivity and anti-oxidant capacity very early in life, which may influence lifespan.