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.

Details

Title
Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice
Author
Mao, Kai 1 ; Gabriela Farias Quipildor 2 ; Tabrizian, Tahmineh 2 ; Novaj, Ardijana 2   VIAFID ORCID Logo  ; Guan, Fangxia 3 ; Walters, Ryan O 1 ; Delahaye, Fabien 4 ; Hubbard, Gene B 5 ; Ikeno, Yuji 6 ; Ejima, Keisuke 7   VIAFID ORCID Logo  ; Li, Peng 8   VIAFID ORCID Logo  ; Allison, David B 7 ; Salimi-Moosavi, Hossein 9 ; Beltran, Pedro J 10 ; Cohen, Pinchas 11 ; Barzilai, Nir 12 ; Huffman, Derek M 1 

1  Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA 
2  Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA 
3  Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA 
4  Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA; Obstetrics and Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, NY, USA 
5  Barshop Institute for Longevity and Aging Studies and Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA 
6  Barshop Institute for Longevity and Aging Studies and Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Geriatric Research, Education & Clinical Center (GRECC), Audie L. Murphy Memorial VA Hospital, San Antonio, TX, USA 
7  School of Health Professions, The University of Alabama at Birmingham, Birmingham, AL, USA; School of Public Health, Indiana University, Bloomington, IN, USA 
8  School of Public Health, The University of Alabama at Birmingham, Birmingham, AL, USA 
9  Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, CA, USA 
10  Oncology Research, Amgen Inc., Thousand Oaks, CA, USA 
11  Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA 
12  Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA 
Pages
1-12
Publication year
2018
Publication date
Jun 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-04805-5
ProQuest document ID
2057088903
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.