Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Neurobiology Programme, Life Sciences Institute, National University of Singapore, Singapore; Yale-NUS College, Science Division, Singapore.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Yale-NUS College, Science Division, Singapore.
Biochem Pharmacol. 2018 Mar;149:91-100. doi: 10.1016/j.bcp.2018.01.030. Epub 2018 Jan 31.
Caloric restriction (CR) is a dietary regimen that aims to reduce the intake of total calories while maintaining adequate supply of key nutrients so as to avoid malnutrition. CR is one of only a small number of interventions that show promising outcomes on health span and lifespan across different species. There is growing interest in the development of compounds that might replicate CR-related benefits without actually restricting food intake. Hydrogen sulfide (HS) is produced inside the bodies of many animals, including humans, by evolutionarily conserved HS synthesizing enzymes. Endogenous HS is increasingly recognized as an important gaseous signalling molecule involved in diverse cellular and molecular processes. However, the specific role of HS in diverse biological processes remains to be elucidated and not all its biological effects are beneficial. Nonetheless, recent evidence suggests that the biological functions of HS intersect with the network of evolutionarily conserved nutrient sensing and stress response pathways that govern organismal responses to CR. Induction of HS synthesizing enzymes appears to be a conserved and essential feature of the CR response in evolutionarily distant organisms, including nematodes and mice. Here we review the evidence for a role of HS in CR and lifespan modulation. HS releasing drugs, capable of controlled delivery of exogenous HS, are currently in clinical development. These findings suggest such HS releasing drugs as a promising novel avenue for the development of CR mimetic compounds.
热量限制（CR）是一种饮食方案，旨在减少总热量的摄入，同时保持关键营养素的充足供应，以避免营养不良。CR 是少数几种在不同物种的健康跨度和寿命方面显示出有希望结果的干预措施之一。人们越来越感兴趣的是开发可能复制 CR 相关益处而实际上不限制食物摄入的化合物。硫化氢（HS）是由进化上保守的 HS 合成酶在许多动物（包括人类）体内产生的。内源性 HS 越来越被认为是一种参与多种细胞和分子过程的重要气态信号分子。然而，HS 在各种生物过程中的具体作用仍有待阐明，并非其所有生物学效应都是有益的。尽管如此，最近的证据表明，HS 的生物学功能与进化上保守的营养感应和应激反应途径网络相交织，这些途径调节了生物体对 CR 的反应。HS 合成酶的诱导似乎是包括线虫和小鼠在内的进化上遥远的生物体对 CR 反应的保守和必需特征。在这里，我们回顾了 HS 在 CR 和寿命调节中的作用的证据。能够控制外源性 HS 释放的 HS 释放药物目前正在临床开发中。这些发现表明，这种 HS 释放药物可能是开发 CR 模拟化合物的有前途的新途径。
