Instituto Nacional de Geriatria, Institutos Nacionales de Salud, D. F., Mexico.
Front Biosci (Landmark Ed). 2014 Jun 1;19(8):1300-19. doi: 10.2741/4283.
Among diverse environmental factors that modify aging, diet has a profound effect. Calorie restriction (CR), which entails reduced calorie consumption without malnutrition, is the only natural regimen shown to extend maximum and mean lifespan, as well as healthspan in a wide range of organisms. Although the knowledge about the biological mechanisms underlying CR is still incipient, various approaches in biogerontology research suggest that CR can ameliorate hallmarks of aging at the cellular level including telomere erosion, epigenetic alterations, stem cells depletion, cellular senescence, mitochondrial dysfunction, genomic instability, proteostasis imbalance, impaired nutrient sensing and abnormal intercellular communication. Currently, the NAD + /sirtuin pathway is one of the few mechanisms described to mediate CR effects and sirtuin-activating compounds (STACs) mimic many effects of CR. Herein, we discuss the effects of CR on healthspan with emphasis on neuroprotection, how CR counteracts cellular aging, how sirtuin pathways intertwine with CR, and the relevance of STACs in mimicking CR effects.
在影响衰老的众多环境因素中，饮食起着深远的作用。热量限制（CR）是一种在不过度营养不良的情况下减少卡路里摄入的方法，它是唯一被证明能延长多种生物的最大寿命、平均寿命和健康寿命的自然方案。尽管关于 CR 背后的生物学机制的知识还处于起步阶段，但生物老年学研究中的各种方法表明，CR 可以改善细胞水平上衰老的标志，包括端粒磨损、表观遗传改变、干细胞耗竭、细胞衰老、线粒体功能障碍、基因组不稳定性、蛋白质平衡失调、营养感应受损和细胞间通讯异常。目前，NAD + /sirtuin 途径是描述介导 CR 效应的少数机制之一，sirtuin-activating compounds (STACs) 模拟了 CR 的许多效应。本文讨论了 CR 对健康寿命的影响，重点是神经保护，CR 如何对抗细胞衰老，sirtuin 途径如何与 CR 交织在一起，以及 STACs 在模拟 CR 效应中的相关性。
