Metabolism plays a significant role in the regulation of aging at different levels, and metabolic reprogramming represents a major driving force in aging. Metabolic reprogramming leads to impaired organismal fitness, an age-dependent increase in susceptibility to diseases, decreased ability to mount a stress response, and increased frailty. The complexity of age-dependent metabolic reprogramming comes from the multitude of levels on which metabolic changes can be connected to aging and regulation of lifespan. This is further complicated by the different metabolic requirements of various tissues, cross-organ communication via metabolite secretion, and direct effects of metabolites on epigenetic state and redox regulation; however, not all of these changes are causative to aging. Studies in yeast, flies, worms, and mice have played a crucial role in identifying mechanistic links between observed changes in various metabolic traits and their effects on lifespan. Here, we review how changes in the organismal and organ-specific metabolome are associated with aging and how targeting of any one of over a hundred different targets in specific metabolic pathways can extend lifespan. An important corollary is that restriction or supplementation of different metabolites can change activity of these metabolic pathways in ways that improve healthspan and extend lifespan in different organisms. Due to the high levels of conservation of metabolism in general, translating findings from model systems to human beings will allow for the development of effective strategies for human health- and lifespan extension.

代谢在不同水平的衰老调控中发挥着重要作用，代谢重编程是衰老的主要驱动力。代谢重编程会导致机体适应性受损、疾病易感性随年龄增长、产生应激反应的能力降低以及虚弱程度增加。年龄依赖性代谢重编程的复杂性来自于代谢变化与衰老和寿命调节相关的众多水平。由于各种组织的不同代谢需求、代谢物分泌的跨器官通讯以及代谢物对表观遗传状态和氧化还原调节的直接影响，这进一步复杂化了。然而，并非所有这些变化都会导致衰老。酵母、苍蝇、蠕虫的研究，小鼠在确定观察到的各种代谢特征变化及其对寿命的影响之间的机制联系方面发挥了至关重要的作用。在这里，我们回顾了有机体和器官特异性代谢组的变化如何与衰老相关，以及靶向特定代谢途径中一百多个不同目标中的任何一个如何延长寿命。一个重要的推论是，限制或补充不同代谢物可以改变这些代谢途径的活性，从而改善不同生物体的健康寿命和延长寿命。由于一般代谢的高度保守性，将模型系统的研究结果转化为人类将有助于制定有效的人类健康和寿命延长策略。