Department of Biology, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Science and Mathematics, Texas A&M University San Antonio, San Antonio, Texas.
Am J Primatol. 2019 Feb;81(2):e22944. doi: 10.1002/ajp.22944. Epub 2018 Dec 26.
Recently, the common marmoset has been proposed as a non-human primate model of aging. Their short lifespan coupled with pathologies that are similar to humans make them an ideal model to understand the genetic, metabolic, and environmental factors that influence aging and longevity. However, many of the underlying physiological changes that occur with age in the marmoset are unknown. Here, we attempt to determine if individual metabolites are predictive of future death and to recapitulate past metabolomic results after a change in environment (move across the country) was imposed on a colony of marmosets. We first determined that low levels of tryptophan metabolism metabolites were associated with risk of death in a 2-year follow-up in the animals, suggesting these metabolites may be used as future biomarkers of mortality. We also discovered that betaine metabolism and methionine metabolism are associated with aging regardless of environment for the animals, or of metabolomic assay technique. These two metabolic pathways are therefore of particular interest to examine as future targets for health and lifespan extending interventions. Many of the pathways associated with age in our first study of marmoset metabolomics were not found to have significant age effects in our second study, suggesting more work is needed to understand the reproducibility of large scale metabolomic studies in mammalian models. Overall, we were able to show that while several metabolomics markers show promise in understanding health and lifespan relationships with aging, it is possible that choice of technique for assay and reproducibility in these types of studies are still issues that need to be examined further.
最近，普通狨猴被提议作为一种非人类灵长类动物衰老模型。它们的寿命较短，并且具有与人类相似的病理特征，这使它们成为了解影响衰老和长寿的遗传、代谢和环境因素的理想模型。然而，狨猴在衰老过程中发生的许多潜在生理变化尚不清楚。在这里，我们试图确定个体代谢物是否可以预测未来的死亡，并在对狨猴群体进行环境改变（跨越大西洋）后，重现过去的代谢组学结果。我们首先确定，在对动物进行 2 年的随访中，色氨酸代谢物水平较低与死亡风险相关，这表明这些代谢物可能被用作未来死亡率的生物标志物。我们还发现，无论动物的环境或代谢组学分析技术如何，甜菜碱代谢和蛋氨酸代谢都与衰老有关。因此，这两种代谢途径特别值得研究，作为健康和延长寿命干预的未来目标。在我们对狨猴代谢组学的第一项研究中，与年龄相关的许多途径在我们的第二项研究中并未发现与年龄有显著影响，这表明需要进一步研究以了解哺乳动物模型中大规模代谢组学研究的可重复性。总体而言，我们能够表明，虽然一些代谢组学标记物在理解与衰老相关的健康和寿命关系方面显示出了希望，但检测技术的选择以及这些类型研究中的可重复性仍然是需要进一步研究的问题。
