Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: Cues for an evolutionarily conserved mechanism of life span control

Massimiliano Bonafè, Michelangela Barbieri, Francesca Marchegiani, Fabiola Olivieri, Emilia Ragno, Claudia Giampieri, Elena Mugianesi, Matteo Centurelli, Claudio Franceschi, Giuseppe Paolisso

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)3299-3304
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number7
DOIs
Publication statusPublished - Jul 1 2003

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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