IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan

Nicole M. Ashpole, Sreemathi Logan, Andriy Yabluchanskiy, Matthew C. Mitschelen, Han Yan, Julie A. Farley, Erik L. Hodges, Zoltan Ungvari, Anna Csiszar, Sixia Chen, Constantin Georgescu, Gene B. Hubbard, Yuji Ikeno, William E. Sonntag

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igff/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

Original languageEnglish (US)
Pages (from-to)129-145
Number of pages17
JournalGeroScience
Volume39
Issue number2
DOIs
StatePublished - Apr 1 2017

Keywords

  • Aging
  • Cancer
  • Insulin-like growth factor-1
  • Longevity
  • Pathology
  • Somatomedin C

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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