Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice

Nat Commun. 2018 Jun 19;9(1):2394. doi: 10.1038/s41467-018-04805-5.

Abstract

Diminished growth factor signaling improves longevity in laboratory models, while a reduction in the somatotropic axis is favorably linked to human aging and longevity. Given the conserved role of this pathway on lifespan, therapeutic strategies, such as insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibodies (mAb), represent a promising translational tool to target human aging. To this end, we performed a preclinical study in 18-mo-old male and female mice treated with vehicle or an IGF-1R mAb (L2-Cmu, Amgen Inc), and determined effects on aging outcomes. Here we show that L2-Cmu preferentially improves female healthspan and increases median lifespan by 9% (P = 0.03) in females, along with a reduction in neoplasms and inflammation (P ≤ 0.05). Thus, consistent with other models, targeting IGF-1R signaling appears to be most beneficial to females. Importantly, these effects could be achieved at advanced ages, suggesting that IGF-1R mAbs could represent a promising therapeutic candidate to delay aging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Aging / metabolism
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Female
  • Humans
  • Longevity / drug effects*
  • Male
  • Mice, Inbred C57BL
  • Motor Activity / drug effects*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / prevention & control
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / immunology
  • Receptor, IGF Type 1 / metabolism
  • Sex Factors
  • Signal Transduction / drug effects*
  • Tumor Burden / drug effects

Substances

  • Antibodies, Monoclonal
  • Receptor, IGF Type 1