Institute of Molecular Biosciences, University of Graz, Graz, Austria; BioTechMed Graz, Graz, Austria.
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
Cell Metab. 2019 Mar 5;29(3):592-610. doi: 10.1016/j.cmet.2019.01.018.
The increase in life expectancy has boosted the incidence of age-related pathologies beyond social and economic sustainability. Consequently, there is an urgent need for interventions that revert or at least prevent the pathogenic age-associated deterioration. The permanent or periodic reduction of calorie intake without malnutrition (caloric restriction and fasting) is the only strategy that reliably extends healthspan in mammals including non-human primates. However, the strict and life-long compliance with these regimens is difficult, which has promoted the emergence of caloric restriction mimetics (CRMs). We define CRMs as compounds that ignite the protective pathways of caloric restriction by promoting autophagy, a cytoplasmic recycling mechanism, via a reduction in protein acetylation. Here, we describe the current knowledge on molecular, cellular, and organismal effects of known and putative CRMs in mice and humans. We anticipate that CRMs will become part of the pharmacological armamentarium against aging and age-related cardiovascular, neurodegenerative, and malignant diseases.
预期寿命的增加使与年龄相关的疾病的发病率超过了社会和经济的可持续性。因此，迫切需要采取干预措施来逆转或至少预防与年龄相关的致病性恶化。在不营养不良的情况下（热量限制和禁食）长期或定期减少热量摄入是唯一可靠地延长哺乳动物（包括非人类灵长类动物）健康寿命的策略。然而，严格和终生遵守这些方案是困难的，这促进了热量限制类似物（CRMs）的出现。我们将 CRMs 定义为通过减少蛋白质乙酰化来促进自噬（一种细胞质回收机制），从而引发热量限制保护途径的化合物。在这里，我们描述了已知和潜在的 CRMs 在小鼠和人类中的分子、细胞和机体效应的最新知识。我们预计，CRMs 将成为对抗衰老以及与衰老相关的心血管、神经退行性和恶性疾病的药理学武器的一部分。
