Aging, oxidative stress and insulin resistance are strongly correlated. There is a growing body of evidence showing that aging is associated with a significant rise in oxidative stress mainly due to a decline in anti-oxidant activity and a rise in pro-oxidant factors such as glucose and insulin concentrations. Furthermore, aging is also associated with a progressive rise in insulin resistance which is due to a complex network of environmental, anthropometric and neuro-hormonal factors. It is noteworthy that extreme longevity, e.g. centenarians, is associated with a low degree of oxidative stress and insulin resistance. The causes for such differences between aged subjects and centenarians is not fully understood. It is likely that a specific genetic background might play a role. However, the insulin gene does not seem to be involved for explaining such age-related differences.