Department of Investigative Pathology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 Japan.
Curr Genomics. 2010 Dec;11(8):562-7. doi: 10.2174/138920210793360934.
Calorie restriction (CR) is the most robust intervention that decreases morbidity and mortality, and thereby increases the lifespan of many organisms. Although the signaling pathways involved in the beneficial effects of CR are not yet fully understood. Several candidate pathways and key molecules have been identified. The effects of CR are highly conserved from lower organisms such as yeast to higher mammals such as rodents and monkeys. Recent studies have also demonstrated beneficial effects of CR in humans, although we need much longer studies to evaluate whether CR also increases the lifespan of humans. In reality, it is difficult for us to conduct CR interventions in humans because the subjects must be kept in a state of hunger and the duration of this state needed to achieve a clinically meaningful effect is still unknown. Thus, research in this field is focusing on the development of molecules that mimic the beneficial effects of CR without reducing food intake. Some of these candidate molecules include plant-derived functional chemicals (phyto-chemicals), synthetic small molecules, and endocrine molecules such as adipokines. Several studies have already shown that this research field may yield novel drugs for the treatment of age-related diseases such as diabetes. In this article, we describe the target pathways, candidate molecules, and strategies to develop CR mimetics.
热量限制（CR）是最有效的干预措施，可以降低发病率和死亡率，从而延长许多生物的寿命。尽管涉及 CR 有益效果的信号通路尚未完全了解，但已经确定了几个候选途径和关键分子。CR 的影响在从酵母等低等生物到啮齿动物和猴子等高等哺乳动物中高度保守。最近的研究还表明 CR 对人类也有有益的影响，尽管我们需要进行更长时间的研究来评估 CR 是否也能延长人类的寿命。实际上，由于受试者必须保持饥饿状态，并且实现临床意义上的效果所需的饥饿状态持续时间尚不清楚，因此我们很难在人类中进行 CR 干预。因此，该领域的研究重点是开发模仿 CR 有益效果而不减少食物摄入的分子。这些候选分子包括植物来源的功能性化学物质（植物化学物质）、合成小分子和内分泌分子，如脂肪因子。一些研究已经表明，这一研究领域可能会产生治疗糖尿病等与年龄相关疾病的新型药物。在本文中，我们描述了开发 CR 模拟物的靶途径、候选分子和策略。
