Hubert David L, Arnold Kenneth R, Greenspan Zachary S, Pupo Anastasia, Robinson Ryan D, Chavarin Valeria V, Barter Thomas B, Djukovic Danijel, Raftery Daniel, Vue Zer, Hinton Antentor, McReynolds Melanie R, Harrison Benjamin R, Phillips Mark A
Department of Integrative Biology, Oregon State University.
Department of Ecology and Evolutionary Biology, University of California, Irvine.
bioRxiv. 2025 Mar 9:2024.06.28.601037. doi: 10.1101/2024.06.28.601037.
Experimental evolution studies that feature selection on life-history characters are a proven approach for studying the evolution of aging and variation in rates of senescence. Recently, the incorporation of genomic and transcriptomic approaches into this framework has led to the identification of hundreds of genes associated with different aging patterns. However, our understanding of the specific molecular mechanisms underlying these aging patterns remains limited. Here, we incorporated extensive metabolomic profiling into this framework to generate mechanistic insights into aging patterns in . Specifically, we characterized metabolomic change over adult lifespan in populations of where selection for early reproduction has led to an accelerated aging phenotype relative to their controls. Using these data we: i) evaluated evolutionary repeatability across the metabolome; ii) assessed the value of the metabolome as a predictor of "biological age" in this system; and iii) identified specific metabolites associated with accelerated aging. Generally, our findings suggest that selection for early reproduction resulted in highly repeatable alterations to the metabolome and the metabolome itself is a reliable predictor of "biological age". Specifically, we find clusters of metabolites that are associated with the different rates of senescence observed between our accelerated aging population and their controls, adding new insights into the metabolites that may be driving the accelerated aging phenotype.
以生活史特征选择为特色的实验进化研究是研究衰老进化和衰老速率变异的一种经证实的方法。最近,将基因组学和转录组学方法纳入这一框架已导致鉴定出数百个与不同衰老模式相关的基因。然而,我们对这些衰老模式背后具体分子机制的理解仍然有限。在这里,我们将广泛的代谢组学分析纳入这一框架,以深入了解衰老模式的机制。具体而言,我们在 种群中表征了成年期寿命内的代谢组变化,在该种群中,相对于其对照,对早期繁殖的选择导致了加速衰老表型。利用这些数据,我们:i)评估了代谢组的进化可重复性;ii)评估了代谢组作为该系统中“生物年龄”预测指标的价值;iii)鉴定了与加速衰老相关的特定代谢物。总体而言,我们的研究结果表明,对早期繁殖的选择导致了代谢组高度可重复的变化,并且代谢组本身是“生物年龄”的可靠预测指标。具体而言,我们发现了与我们的加速衰老种群及其对照之间观察到的不同衰老速率相关的代谢物簇,为可能驱动加速衰老表型的代谢物提供了新的见解。