Development of calorie restriction mimetics as therapeutics for obesity, diabetes, inflammatory and neurodegenerative diseases.
Development of calorie restriction mimetics as therapeutics for obesity, diabetes, inflammatory and neurodegenerative diseases.
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DOI：
10.2174/138920210793360934
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发表时间：
2010-12
期刊：
影响因子：
2.6
通讯作者：
Shimokawa I
中科院分区：
文献类型：
--
作者：
Chiba T;Tsuchiya T;Komatsu T;Mori R;Hayashi H;Shimokawa I
热量限制（CR）是降低发病率和死亡率的最有力的干预措施，从而延长许多生物体的寿命。尽管参与CR有益作用的信号通路尚未完全了解。已经确定了几个候选途径和关键分子。CR的作用从低等生物如酵母到高等哺乳动物如啮齿动物和猴子是高度保守的。最近的研究也证明了CR对人类的有益作用，尽管我们需要更长的研究来评估CR是否也会延长人类的寿命。实际上，我们很难在人类中进行CR干预，因为受试者必须处于饥饿状态，并且实现临床有意义的效果所需的这种状态的持续时间仍然未知。因此，该领域的研究集中在开发模拟CR有益作用而不减少食物摄入的分子。这些候选分子中的一些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有关的疾病的新药。在这篇文章中，我们描述了目标途径，候选分子，和策略，以开发CR模拟物。
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.
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