The impact of chronic caloric restriction (CR) on health and survival is complex with poorly understood underlying molecular mechanisms. A recent study in mice addressing the diets used in nonhuman primate CR studies found that while diet composition did not impact longevity, fasting time and total calorie intake were determinant for increased survival. Here, integrated analysis of physiological and multi-omics data from ad libitum, meal-fed, or CR animals was used to gain insight into pathways associated with improved health and survival. We identified a potential involvement of the glycine-serine-threonine metabolic axis in longevity and related molecular mechanisms. Direct comparison of the different feeding strategies unveiled a pattern of shared pathways of improved health that included short-chain fatty acids and essential PUFA metabolism. These findings were recapitulated in the serum metabolome from nonhuman primates. We propose that the pathways identified might be targeted for their potential role in healthy aging.

慢性热量限制 (CR) 对健康和生存的影响是复杂的，其潜在的分子机制知之甚少。最近一项针对非人类灵长类动物 CR 研究中使用的饮食的小鼠研究发现，虽然饮食成分不会影响寿命，但禁食时间和总卡路里摄入量是提高生存率的决定因素。在这里，来自随意的生理和多组学数据的综合分析、膳食喂养或 CR 动物被用来深入了解与改善健康和生存相关的途径。我们确定了甘氨酸-丝氨酸-苏氨酸代谢轴在长寿和相关分子机制中的潜在参与。不同喂养策略的直接比较揭示了改善健康的共享途径模式，包括短链脂肪酸和必需的多不饱和脂肪酸代谢。这些发现在非人类灵长类动物的血清代谢组中得到了概括。我们建议确定的途径可能针对它们在健康老龄化中的潜在作用。