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Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity.

ABSTRACT: Attenuated growth hormone and insulin-like growth factor-1 (GH/IGF-1) signaling is associated with extended lifespan in several animal models. However, the effect of diminished GH/IGF-1 activity on survival in humans has not been confirmed. We tested the hypothesis that IGF-1 levels in nonagenarians (n = 184), measured at study enrollment, predict the duration of their incremental survival. In the Kaplan-Meier analysis, females with IGF-1 levels below the median (≤ 96 ng mL(-1) ) had significantly longer survival compared with females with levels above the median, P < 0.01. However, this survival advantage was not observed in males (P = 0.83). On the other hand, in both males and females with a history of cancer, lower IGF-1 levels predicted longer survival (P < 0.01). IGF-1 level remained a significant predictor of survival duration in linear regression models after multivariable adjustment in females (P = 0.01) and individuals with a history of cancer (P < 0.01). We show for the first time that low IGF-1 levels predict life expectancy in exceptionally long-lived individuals.

SUBMITTER: Milman S

PROVIDER: S-EPMC4116456 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionIGF-1 (insulin-like growth factor-1) is a hormone involved in cell growth and other important processes. In the kidney, IGF-1 has a stimulating effect, increasing the blood flow and glomerular filtration rate. Although many experimental animal studies regarding the role of IGF-1 in the kidney have been conducted, few human studies are available in the literature. Obesity is a cause of renal failure, and several glomerular lesions associated with obesity have been described. However, no studies regarding the levels of IGF-1 in morbidly obese patients with renal injury associated with obesity have been conducted.AimTo determine the serum IGF-1 concentrations in morbidly obese patients with normal renal function but with different types of early obesity-related glomerular lesions and to evaluate the possible relationship between IGF-1 and the presence of renal lesions.MethodsEighty morbidly obese patients with renal biopsy, including 11 patients with no evidence of renal lesion, 17 patients with single glomerulomegaly, 21 patients with single podocyte hypertrophy, 10 patients with glomerulomegaly and podocyte hypertrophy, 5 patients with focal segmental hyalinosis, and 16 patients with increased mesangial matrix and/or mesangial proliferation, participated in this study. Biological parameters, including serum IGF-1 concentrations with the standard deviation score for age (SDS-IGF-1), were determined for all patients.ResultsEighty patients (50 women and 30 men) with a mean BMI of 52.63 ± 8.71 and a mean age of 42.40 ± 9.45 years were included in this study. IGF-1, IGF-1 SDS and IGF-1BP3 levels according to the renal injury were compared (normal glomeruli: IGF-1 = 190.17 ± 72.46; glomerulomegaly: IGF-1 = 122.3 ± 50.05; podocyte hypertrophy: IGF-1 = 119.81 ± 60.34; focal segmental hyalinosis: IGF-1 170.98 ± 100.83, increased mesangial matrix and/or mesangial proliferation: IGF-1 117.73 ± 63.87). Statistically significant differences were observed between serum levels of IGF-1 and between the levels of SDS-IGF-1 by comparing the group without glomerular lesion with the group formed by patients with any type of glomerular injury. Logistic regression analysis was performed, with the dependent variable defined as the glomerular injury. In the multivariate analysis, only SDS-IGF-1 was associated with glomerular injury, and low levels of IGF-1 SDS were a risk factor for kidney injury.ConclusionsOur study demonstrates that low IGF-1 serum levels are associated with renal lesions in morbidly obese patients without overt clinical renal manifestations.

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Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity.

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