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

Author

Listed:
  • Kai Mao

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Gabriela Farias Quipildor

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Tahmineh Tabrizian

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Ardijana Novaj

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Fangxia Guan

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Ryan O. Walters

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Fabien Delahaye

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Gene B. Hubbard

    (University of Texas Health Science Center at San Antonio)

  • Yuji Ikeno

    (University of Texas Health Science Center at San Antonio
    Audie L. Murphy Memorial VA Hospital)

  • Keisuke Ejima

    (The University of Alabama at Birmingham
    Indiana University)

  • Peng Li

    (The University of Alabama at Birmingham)

  • David B. Allison

    (The University of Alabama at Birmingham
    Indiana University)

  • Hossein Salimi-Moosavi

    (Amgen Inc.)

  • Pedro J. Beltran

    (Oncology Research, Amgen Inc.)

  • Pinchas Cohen

    (University of Southern California)

  • Nir Barzilai

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Derek M. Huffman

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

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.

Suggested Citation

  • 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, 2018. "Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04805-5
    DOI: 10.1038/s41467-018-04805-5
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    Cited by:

    1. Omid Omrani & Anna Krepelova & Seyed Mohammad Mahdi Rasa & Dovydas Sirvinskas & Jing Lu & Francesco Annunziata & George Garside & Seerat Bajwa & Susanne Reinhardt & Lisa Adam & Sandra Käppel & Nadia D, 2023. "IFNγ-Stat1 axis drives aging-associated loss of intestinal tissue homeostasis and regeneration," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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