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.

学界普遍认为衰老与分子损伤增加密切相关，但衰老的代表性标志物会因实验条件与生物体种类的不同而存在差异，这使得难以评估整个生命周期内累积损伤的相关特征。本研究采用非靶向代谢组学分析（nontargeted metabolite profiling），对喂食正常对照饮食与延长寿命饮食的果蝇体内超过15000种代谢物的年龄相关变化轨迹进行追踪。研究结果显示，衰老过程伴随代谢物多样性提升与低丰度分子增多，提示这类分子中包含累积产生的损伤。值得注意的是，检测到的化合物数量在生命后期趋于平稳，这一变化模式与果蝇存活率密切相关。14%的代谢物表现出年龄相关的丰度变化，这类变化在生命后期以及长寿果蝇中出现减缓。与之相反，已注释的已知代谢物的丰度变化模式与非靶向检测到的代谢物及转录本相似，但并未出现多样性提升的情况。靶向代谢组学分析（targeted profiling）同样揭示了代谢速率减缓以及寿命限制分子的积累。综上，衰老的核心特征是代谢组的渐进式重塑，而这种重塑受实验条件影响且在高龄阶段出现减缓，这一过程与死亡率及分子损伤密切相关。