Association between Genetic Variations in the Insulin/Insulin-Like Growth Factor (Igf-1) Signaling Pathway and Longevity: A Systematic Review and Meta-Analysis

ISSN: 1875-6212 (Online)
ISSN: 1570-1611 (Print)

Volume 15, 6 Issues, 2017

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Current Vascular Pharmacology

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Dimitri P. Mikhailidis
Academic Head, Department of Clinical Biochemistry
Royal Free Hospital Campus
University College London Medical School
University College London (UCL)
Pond Street
London, NW3 2QG

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Association between Genetic Variations in the Insulin/Insulin-Like Growth Factor (Igf-1) Signaling Pathway and Longevity: A Systematic Review and Meta-Analysis

Current Vascular Pharmacology, 12(5): 674-681.

Author(s): Danilo Di Bona, Giulia Accardi, Claudia Virruso, Giuseppina Candore and Calogero Caruso.

Affiliation: U.O. di Medicina Trasfusionale, AOUP Paolo Giaccone, Via del Vespro 129, 90127 Palermo, Italy.


Some studies have shown that polymorphisms in the insulin growth factor-1 (IGF-1) signaling pathway genes could influence human longevity. However, the results of different studies are often inconsistent. Our aim was to investigate by systematic review and meta-analysis the association of the common polymorphisms defining the genetic variability of the IGF-1 signaling pathway associated with human longevity. Eleven studies investigating the association between the polymorphisms in the IGF-1 signaling pathway genes (IGF-1, IGF-1 receptor (IGF-1R), Forkhead box O3A (FOXO3A) and Silent mating type Information Regulation 1 (SIRT1) and longevity were found and analyzed. The modelfree approach was applied to meta-analyze these studies. No association was reported between the single nucleotide polymorphisms (SNPs) of IGF-1 and longevity in the only available study. The meta-analysis of available data from four studies, showed a significant association with the IGF-1R polymorphism rs2229765, suggesting that subjects with the Abearing genotype have a greater chance of longevity. Concerning the five studies on FOXO3A SNPs, for the rs2764264 a significant association with longevity was observed for C allele when only males were included in the analysis. Statistically significant results were obtained for other SNPs as well, i.e. rs2802292 (G allele), rs9400239 and rs479744 (T and A alleles, respectively). For rs9400239 the association was observed in long lived males with a lower odds ratio than in centenarians, while in rs479744 a significant association was highlighted in centenarians. Concerning SIRT1, no association between the SNPs under study and longevity was observed in the only available report. Current findings suggest that both IGF-1R and FOXO3A polymorphisms could be associated with longevity. The high degree of between-study heterogeneity and the low number of available studies underline the need for further methodologically adequate analyses to confirm this evidence.


FOXO3A, IGF-1; IGF-1R, longevity, meta-analysis, SIRT1, SNP.

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Article Details

Volume: 12
Issue Number: 5
First Page: 674
Last Page: 681
Page Count: 8
DOI: 10.2174/1570161111666131218152807
Price: $58

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