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Related Experiment Videos

Reduced insulin/IGF-1 signalling and human longevity.

Diana van Heemst1, Marian Beekman, Simon P Mooijaart

  • 1Section of Gerontology and Geriatrics, Department of General Internal Medicine, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands. D.van_Heemst@lumc.nl

Aging Cell
|March 18, 2005
PubMed
Summary

Aging is linked to the insulin/IGF-1 signalling (IIS) pathway. In women, reduced IIS activity is associated with shorter stature and increased longevity, suggesting a beneficial role for genetic variation.

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Area of Science:

  • Genetics
  • Gerontology
  • Endocrinology

Background:

  • Aging is hormonally regulated by the evolutionarily conserved insulin/IGF-1 signalling (IIS) pathway.
  • Mutations in IIS components influence lifespan and oxidative stress resistance in model organisms.
  • IIS's effect on longevity is often sex-specific, particularly in females.

Purpose of the Study:

  • To investigate the relationship between IIS pathway activity, body height, and longevity in humans.
  • To analyze the impact of genetic variants in IIS pathway components on human lifespan and body size.
  • To determine if reduced IIS signalling is associated with improved survival in older age.

Main Methods:

  • Prospective follow-up study analyzing human genetic variants in IIS pathway components (GHRHR, GH1, IGF1, INS, IRS1).

Related Experiment Videos

  • Calculation of composite IIS scores to estimate pathway activity based on variant effects.
  • Multivariate analyses to assess the impact of separate variants and IIS scores on lifespan and body size.

    • Main Results:

    • Lower composite IIS scores in women were significantly associated with reduced body height and enhanced old age survival.
    • Multivariate analyses highlighted the GH1 SNP, IGF1 CA repeat, and IRS1 SNP as key contributors.
    • Female carriers of the GH1 SNP variant allele had 2 cm shorter stature and a 0.80-fold reduced mortality risk.

    Conclusions:

    • Genetic variation leading to reduced insulin/IGF-1 signalling activation is beneficial for longevity in human females.
    • This effect is more pronounced for the GH1 SNP compared to other conserved IIS genes.
    • Reduced IIS signalling and its association with shorter stature may represent an adaptive mechanism for improved survival in aging women.