Advancing age and insulin resistance: new facts about an ancient history.

The relationship between advancing age and insulin resistance is widely known, but the cause(s) of such association are less well understood. Age-related changes in anthropometric characteristics and environmental factors (changes in diet habits and decline in physical activity) have been hypothesized as being among the main causes. More recently, the role of plasma insulin-like growth factor I (IGF-I), dehydroepiandrosterone sulphate (DHEAS) and tumour necrosis factor alpha (TNF-alpha) concentrations as well as the degree of oxidative stress have also been evaluated. As far as the anthropometric changes are concerned, a decline in fat-free mass and a relative or absolute increase in fat mass are common findings in aged subjects. Such changes are combined with a decline in plasma DHEAS and IGF-I concentration and a rise in plasma TNF-alpha concentrations and oxidative stress, which, in turn, may interact with the anthropometric changes determining the worsening in insulin-mediated glucose uptake. Finally, age-related environmental factors (changes in diet quality and decline in the degree of physical activity) might be a common factor allowing anthropometric factors and age-related remodelling to accelerate their negative impact on insulin action.