Data from: Age- and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation

Aging is thought to be associated with increased molecular damage, but representative markers vary across conditions and organisms, making it difficult to assess properties of cumulative damage throughout lifespan. We used nontargeted metabolite profiling to follow age-associated trajectories of >15,000 metabolites in Drosophila subjected to control and lifespan-extending diets. We find that aging is associated with increased metabolite diversity and low-abundance molecules, suggesting they include cumulative damage. Remarkably, the number of detected compounds leveled-off in late-life, and this pattern associated with survivorship. Fourteen-percent of metabolites showed age-associated changes, which decelerated in late-life and long-lived flies. In contrast, known metabolites changed in abundance similarly to nontargeted metabolites and transcripts, but did not increase in diversity. Targeted profiling also revealed slower metabolism and accumulation of lifespan-limiting molecules. Thus, aging is characterized by gradual metabolome remodeling, and condition- and advanced age-associated deceleration of this remodeling is linked to mortality and molecular damage.

现有研究认为，衰老与分子损伤加剧存在关联，但代表性标志物会因实验条件和生物物种的不同而存在差异，这使得研究者难以评估整个生命周期内累积损伤的各项属性。本研究采用非靶向代谢谱分析（nontargeted metabolite profiling）技术，对喂食正常对照饮食与延寿饮食的果蝇（Drosophila）体内超过15000种代谢物的衰老相关变化轨迹进行了追踪。研究发现，衰老与代谢物多样性提升以及低丰度分子增多显著相关，这提示此类分子中包含累积损伤成分。值得注意的是，检测到的化合物数量在衰老后期趋于平稳，且这一变化模式与果蝇存活率密切相关。14%的代谢物呈现出衰老相关的丰度变化，这类变化在衰老后期以及长寿果蝇体内均出现减缓趋势。与之形成对比的是，已知代谢物的丰度变化模式与非靶向检测得到的代谢物及转录本（transcripts）相似，但其多样性并未出现提升。靶向代谢谱分析同样揭示了代谢速率减缓以及寿命限制分子的累积现象。综上，衰老的核心特征为代谢组（metabolome）的渐进式重塑，而该重塑过程随实验条件变化以及衰老晚期出现的减速现象，与果蝇死亡率及分子损伤密切相关。