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 and Derek M. Huffman ()
Additional contact information
Kai Mao: Albert Einstein College of Medicine
Gabriela Farias Quipildor: Albert Einstein College of Medicine
Tahmineh Tabrizian: Albert Einstein College of Medicine
Ardijana Novaj: Albert Einstein College of Medicine
Fangxia Guan: Albert Einstein College of Medicine
Ryan O. Walters: Albert Einstein College of Medicine
Fabien Delahaye: 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
Keisuke Ejima: The University of Alabama at Birmingham
Peng Li: The University of Alabama at Birmingham
David B. Allison: The University of Alabama at Birmingham
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
Derek M. Huffman: Albert Einstein College of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04805-5

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