Serum insulin-like growth factor I (IGF-I) : functional ability and cognitive status in centenarians and centenarians offspring

Several evidences suggest that IGF-I system regulates healthy aging and human longevity. While in animal models alterations of IGF-I signalling increase the life expectancy, in humans there are few contradictory data on this topic. Low levels of serum IGF-I have been detected in populations of centenarians and have protective effects on the risk of several cancers in the general population. On the other hand, in the elderly population relatively high circulating IGF-I levels are associated with a decrease in cardiovascular morbidity and mortality. Centenarians are an extraordinary model to study human longevity and to identify their biological determinants. However, there are several inherent disadvantages in the study of centenarians: rarity, presence of frailty due to extreme age and lack of a control group of the same age. The presence of an age-matched control group is crucial in studies evaluating IGF system, considering that age influences IGF-I production. Centenarians' offspring, for whom it is possible to identify an appropriate control group (subjects of the same age born from non long-lived parents), appear to be a new and promising model of human longevity, showing a higher probability to became long-living. The aim of the present study was to evaluate the role of IGF-I in the modulation of functional ability and cognitive status in elderly subjects, particularly in centenarians and in potentially long-living population. In Milan we recruited: 48 centenarians; 28 centenarians' offspring born from one centenarian parent (O150), 21 centenarians' offspring born from both long-lived parents, one centenarian and the other long-lived (O250); 21 control subjects who do not have long-lived parents. In all subjects we evaluated serum IGF-I levels, self-sufficiency and autonomy (Activities of Daily Living: ADL; Instrumental Activities of Daily Living: IADL) and cognitive ability (Mini Mental Status Examination: MMSE; Mini Mental Status Examination corrected for age and education: MMSEc. IGF-I was significantly lower in centenarians (p<0.001) compared to controls. No significant differences in age and serum IGF-I levels were found between O150, O250 and controls. ADL, IADL, MMSE and MMSEc resulted to be significantly lower (p<0.001) in centenarians than in controls, while no significant differences were observed for all previous parameters between O150, O250 and controls. In the pooled groups IGF-I positively correlated with ADL (r=0.38, p<0.0001), IADL (r=0.42, p<0.0001), MMSE (r=0.40, p<0.0001) and MMSEc (r=0.30, p=0.001). In conclusion, these data suggest that IGF-I system may play an important protective role in the age-related decline of cognitive performance and functional ability.