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 - Funding Information:
This work was supported by the NIA (R00AG037574 and R56AG052981), the Prevent Cancer Foundation, the American Institute for Cancer Research (AICR), the American Federation for Aging Research (AFAR) and Einstein Startup Funds to D.M.H.; NIA P01AG021654, P30AG038072, R37AG18381 and the Paul Glenn Foundation for Medical Research to N.B.; NIH R01GM090311, R01ES020812 and P01AG034906 to P.C.; NIA P30AG013319 to Y.I. and G.B.H., P30AG050886 to D.B.A. This work was also supported by the Einstein-Sinai Diabetes Research Center (P30DK20541). R.O.W. and T.T. are supported by a T32 Training Grant (T32AG23475). We also acknowledge the Einstein Computational Genomic Core for its support, and the NCI supported Einstein Cancer Center (P30CA013330). We finally acknowledge Drs. Charles Glaus and Rick Jacobsen at Amgen Inc for their valuable input and Amgen Inc for material support of L2-Cmu.
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 -