Role of IGF1 system in human longevity. A study in a wide population of centenarians and centenarians offspring
G Vitale1,2, M P Brugts3, G Ogliari1,4, D Castaldi2, L M Fatti2, L J Hofland3, D Monti5, F Cavagnini1,2, C Franceschi6, D Mari1,4 & J A M J L Janssen3
Increasing evidence has recently accumulated suggesting that IGF1 system is involved in the regulation of longevity. While in animal models alterations of IGF1 signalling increase life expectancy, in humans there are contradictory data. Centenarians are an extraordinary model to study human longevity, however, they present a number of drawbacks: rarity, frailty due to extreme age and lack of a control group of the same age. The availability of an age-matched control group is crucial in studies evaluating IGF system, considering that age impacts on IGF1 production. Centenarians offspring, for whom it is possible to obtain an appropriate control group (subjects of same age born from not long-lived parents), represent a new model of longevity, showing a lower morbidity and mortality. The aim of the present study was to investigate the role of IGF1 in the modulation of longevity. We recruited: 106 centenarians, 192 centenarians offspring and 80 offspring of both non long-lived parents (controls) living in Northern Italy. No significant difference in age was observed between centenarians offspring and controls. Serum total IGF1 levels and IGF1 bioactivity, using an in-house KIRA assay, were evaluated in all subjects. Mean serum total IGF1 values were significantly lower in centenarians compared to centenarians offspring and controls (both P<0.0001). IGF1 levels were lower in centenarians offspring than controls (P=0.002). Circulating IGF1 bioactivity were lower in centenarians and their offspring than in controls (P<0.001 and P=0.002, respectively), while no significant difference was observed between centenarians and centenarians offspring. Interestingly, these differences in total IGF1 and IGF1 bioactivity between centenarians offspring and controls remained significant after correction for age, gender and BMI (both P=0.001). In conclusion, these data strongly support a role of IGF1 system in the modulation of human aging and longevity.