Hubert, D. L.; Arnold, K. R.; Greenspan, Z. G.; Pupo, A.; Robinson, R. D.; Chavarin, V. V.; Barter, T. T.; Djukovic, D.; Raftery, D.; Vue, Z.; Hinton, A.; McReynolds, M. R.; Harrison, B. R.; Phillips, M. A.

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 Drosophila melanogaster. Specifically, we characterized metabolomic change over time associated with accelerated aging in populations of D. melanogaster under selection for early reproduction compared to their controls. Using this data we: i) evaluated the evolutionary repeatability across the metabolome; ii) evaluated the value of the metabolome as a predictor of biological age in this system; and iii) identified specific metabolic pathways associated with accelerated aging. Generally, our findings suggest that the metabolome is a reliable predictor of age and senescence in populations that share a recent evolutionary history. Metabolomic analysis revealed that generations of selection for early reproduction resulted in highly repeatable alterations to the metabolome. Specifically, changes in carbohydrate, amino acid, and TCA cycle-related metabolite abundances over time point to metabolic remodeling that favors rapid early reproduction with long-term consequences for carbohydrate and protein utilization.