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.

中文翻译：

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IGF-1受体的后期靶向可改善雌性小鼠的健康寿命和寿命。

生长因子信号转导的减少可延长实验室模型的寿命，而生长激素轴的减少则有利于人类衰老和延长寿命。考虑到该途径在生命中的保守作用，诸如胰岛素样生长因子1受体（IGF-1R）单克隆抗体（mAb）之类的治疗策略代表了针对人类衰老的有前途的翻译工具。为此，我们在接受媒介物或IGF-1R mAb（L2-Cmu，Amgen Inc）治疗的18个月大的雄性和雌性小鼠中进行了临床前研究，并确定了其对衰老结果的影响。在这里，我们显示L2-Cmu优先改善女性健康状况，并使女性的中位寿命延长9％（P = 0.03），同时减少肿瘤和炎症（P≤0.05）。因此，与其他模型一致，靶向IGF-1R信号传导似乎对女性最有益。重要的是，这些作用可以在高龄时实现，这表明IGF-1R mAbs可以代表一种有希望的延缓衰老的治疗药物。