TY - JOUR
T1 - Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice
AU - Mao, Kai
AU - Quipildor, Gabriela Farias
AU - Tabrizian, Tahmineh
AU - Novaj, Ardijana
AU - Guan, Fangxia
AU - Walters, Ryan O.
AU - Delahaye, Fabien
AU - Hubbard, Gene B.
AU - Ikeno, Yuji
AU - Ejima, Keisuke
AU - Li, Peng
AU - Allison, David B.
AU - Salimi-Moosavi, Hossein
AU - Beltran, Pedro J.
AU - Cohen, Pinchas
AU - Barzilai, Nir
AU - Huffman, Derek M.
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-04805-5
DO - 10.1038/s41467-018-04805-5
M3 - Article
C2 - 29921922
AN - SCOPUS:85048756857
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2394
ER -