期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-04805-5
关键词
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资金
- NIA [R00AG037574, R56AG052981, P30AG013319, P30AG050886, P01AG021654, P30AG038072, R37AG18381]
- Prevent Cancer Foundation
- American Institute for Cancer Research (AICR)
- American Federation for Aging Research (AFAR)
- Einstein Startup Funds
- Paul Glenn Foundation for Medical Research
- NIH [R01GM090311, R01ES020812, P01AG034906]
- Einstein-Sinai Diabetes Research Center [P30DK20541]
- Einstein Computational Genomic Core
- NCI [P30CA013330]
- [T32AG23475]
- NATIONAL CANCER INSTITUTE [P30CA013330] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK026687, P30DK020541] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES020812] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM090311] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [T32AG023475, P01AG034906, P01AG055369, P30AG038072, P30AG013319, P01AG021654, R00AG037574, R56AG052981, P30AG050886, R37AG018381] Funding Source: NIH RePORTER
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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