Deregulation of the inflammatory response plays a major role in the age-related decline of physical performance. The causal pathway leading from inflammation to disability has not been fully clarified, but several researches suggest that interleukin-6 (IL-6) causes a reduction of physical performance in elderly through its effect on muscle function. In vitro studies demonstrated that IL-6 inhibits the secretion of insulin-like growth factor I (IGF-I) and its biological activity, suggesting that the negative effect of IL-6 on muscle function might be mediated through IGF-I. We evaluated the joint effect of IGF-I and IL-6 on muscle function in a population-based sample of 526 persons with a wide age range (20–102 yr). After adjusting for potential confounders, such as age, sex, body mass index, IL-6 receptor, and IL-6 promoter polymorphism, IL-6, IGF-I, and their interaction were significant predictors of handgrip and muscle power. In analyses stratified by IL-6 tertiles, IGF-I was an independent predictor of muscle function only in subjects in the lowest IL-6 tertile, suggesting that the effect of IGF-I on muscle function depends on IL-6 levels. This mechanism may explain why IL-6 is a strong risk factor for disability.

Current literature indicates that abrogation of the IGF-I response pathway affects longevity in Caenorhabditis elegans, and that the down-regulation of IGF-I gene expression is associated with an extension of the life span in mice. In this paper we tested the hypothesis that polymorphic variants of IGF-I response pathway genes, namely IGF-IR (IGF-I receptor; G/A, codon 1013), PI3KCB (phosphoinositol 3-kinase; T/C, -359 bp; A/G, -303 bp), IRS-1 (insulin receptor substrate-1; G/A, codon 972), and FOXO1A (T/C, +97347 bp), play a role in systemic IGF-I regulation and human longevity. The major finding of this investigation was that subjects carrying at least an A allele at IGF-IR have low levels of free plasma IGF-I and are more represented among long-lived people. Moreover, genotype combinations at IGF-IR and PI3KCB genes affect free IGF-I plasma levels and longevity. These findings represent the first indication that free IGF-I plasma levels and human longevity are coregulated by an overlapping set of genes, contributing to the hypothesis that the impact of the IGF-I/insulin pathway on longevity is a property that has been evolutionarily conserved throughout the animal kingdom.

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The clinical association of insulin resistance (IR), hypertension, obesity, dyslipidaemia (increased VLDL and decreased HDL-cholesterol concentration in plasma), higher plasma PAI ±1 concentrations and decreased arterial distensibility, is widely known as the insulin resistance syndrome [1±3]. A strong association between the occurrence of insulin resistance syndrome and cardiovascular diseases (mainly coronary heart diseases) has been also demonstrated [1±2]. Nevertheless, hyperinsulinaemia is also in itself an independent risk factor for cardiovascular diseases Abstract Aim/hypothesis. Previous studies have shown that insulin has an important in vitro role in the regulation of human erythropoiesis. We investigated whether in vivo hyperinsulinaemia/insulin resistance affects haematological parameters. Methods. A total of 608 subjects between 22 and 99 years of age were enrolled in the Chianti study, an epidemiological study of factors affecting mobility in old age. The degree of insulin resistance was assessed using the homeostasis model. Results. We found a correlation between insulin resistance and red blood cell count, (r = 0.14 p < 0.001), plasma haemoglobin (r = 0.16 p < 0.001), haematocrit (r = 0.15 p < 0.001) and plasma iron (r = 0.1 p < 0.05) concentrations. Red blood cell count was also associated with the other biological markers of insulin resistance syndrome. Subjects with higher insulin resistance (4 quartile) had higher red blood cell count, plasma triglycerides and low density lipoproteins (LDL) cholesterol concentrations and lower high density lipoproteins (HDL) cholesterol concentrations then subjects at the lowest quartiles of insulin resistance. Insulin resistance and BMI were significant and independent predictors of red blood cell count even when the analysis was adjusted for age, sex, waist-to-hip ratio, plasma iron and drug intake. Conclusion/hypothesis. Our findings provide in vivo evidence of a relation between hyperinsulinaemia/insulin resistance, the main variables of insulin resistance syndrome and erythropoiesis. Increased red blood cell count could be considered as a new aspect of the insulin resistance syndrome that could contribute to the increased risk of developing cardiovascular problems. [Diabetologia (2001