Age-related insulin resistance: is it an obligatory finding? The Lesson from healthy centenarians

It is widely known that advancing age is associated with impaired glucose h andling. A unifying hypothesis explaining the relationship between aging an d insulin resistance might encompass four main pathways, namely: (a) anthro pometric changes (relative and absolute increase in body fat combined with a decline in fat free mass) which could be the anatomic substrate for expla ining the reduction in active metabolic tissue; (b) environmental causes, m ainly diet style and physical activity; (c) neuro-hormonal variations [decl ine in plasma dehydroepandrosterone sulphate (DHEAS) and IGF-1]; and finall y (d) the rise in oxidative stress. Indeed previous studies have also inves tigated the occurrence and the degree of insulin resistance in healthy cent enarians. Such data demonstrated that age-related insulin resistance is not an obligatory finding in the elderly and that healthy centenarians have a preserved insulin action compared to aged subjects. Why insulin action is p reserved in centenarians is still not known. Nevertheless, a possible appro ach to the question is to outline the centenarians' anthropometric, endocri ne and metabolic characteristics in order to design a clinical picture of s uch metabolic 'successful aging'. According to the remodeling theory of age , the preserved insulin action in centenarians might be the net result of t he continuous adaptation of the body to the deleterious changes that occur over time. Nevertheless, only future longitudinal studies specifically desi gned to investigate the relationship between extreme old age and degree of insulin sensitivity will provide a conclusive answer with regard to the pat hophysiology of adaptive metabolic changes occurring in the elderly. Copyri ght (C) 2001 John Wiley & Sons, Ltd.