Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Aging Cell. 2013 Aug;12(4):645-51. doi: 10.1111/acel.12088. Epub 2013 Jun 5.
Caloric restriction (CR) and down-regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here, we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR induces dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals. Finally, in both rats and humans, CR evoked similar responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with longevity: IGF-1/insulin signaling, mitochondrial biogenesis, and inflammation. Furthermore, our data identify promising pathways for therapeutic targets to combat age-related diseases and promote health in humans.
热量限制（CR）和下调胰岛素/IGF 通路是已知的最有效的干预措施，可以延长低等生物的寿命。然而，关于 CR 诱导的人类分子适应性知之甚少。在这里，我们报告说，人类的长期 CR 抑制了骨骼肌中的 IGF-1/胰岛素通路，这是一种关键的代谢组织。我们还证明，CR 诱导了骨骼肌转录谱的剧烈变化，类似于年轻人的转录谱。最后，在大鼠和人类中，CR 在骨骼肌的转录谱中引起了类似的反应。这种共同的特征包括与长寿相关的三个关键途径：IGF-1/胰岛素信号、线粒体生物发生和炎症。此外，我们的数据确定了有希望的治疗靶点途径，以对抗与年龄相关的疾病并促进人类健康。
