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

Kai Mao, Gabriela Farias Quipildor, Tahmineh Tabrizian, Ardijana Novaj, Fangxia Guan, Ryan O. Walters, Fabien Delahaye, Gene B. Hubbard, Yuji Ikeno, Keisuke Ejima, Peng Li, David B. Allison, Hossein Salimi-Moosavi, Pedro J. Beltran, Pinchas Cohen, Nir Barzilai, Derek M. Huffman

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Article number2394
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Mao, K., Quipildor, G. F., Tabrizian, T., Novaj, A., Guan, F., Walters, R. O., Delahaye, F., Hubbard, G. B., Ikeno, Y., Ejima, K., Li, P., Allison, D. B., Salimi-Moosavi, H., Beltran, P. J., Cohen, P., Barzilai, N., & Huffman, D. M. (2018). Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice. Nature communications, 9(1), [2394]. https://doi.org/10.1038/s41467-018-04805-5