It has been recognized for nearly a century that diet modulates aging. Despite early experiments suggesting that reduced caloric intake augmented lifespan, accumulating evidence indicates that other characteristics of the diet may be equally or more influential in modulating aging. We demonstrate that behavior, metabolism, and lifespan in Drosophila are affected by whether flies are provided a choice of different nutrients or a single, complete medium, largely independent of the amount of nutrients that are consumed. Meal choice elicits a rapid metabolic reprogramming that indicates a potentiation of TCA cycle and amino acid metabolism, which requires serotonin 2A receptor. Knockdown of glutamate dehydrogenase, a key TCA pathway component, abrogates the effect of dietary choice on lifespan. Our results reveal a mechanism of aging that applies in natural conditions, including our own, in which organisms continuously perceive and evaluate nutrient availability to promote fitness and well-being.

中文翻译：

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5-羟色胺 2A 受体信号协调中央代谢过程以调节衰老以响应营养选择

近一个世纪以来，人们已经认识到饮食可以调节衰老。尽管早期的实验表明减少热量摄入可以延长寿命，但越来越多的证据表明饮食的其他特征可能对调节衰老具有同等或更大的影响。我们证明，果蝇的行为、新陈代谢和寿命会受到是否为苍蝇提供不同营养选择或单一、完整培养基的影响，这在很大程度上与消耗的营养量无关。膳食选择引发快速代谢重编程，这表明 TCA 循环和氨基酸代谢增强，这需要血清素 2A 受体。谷氨酸脱氢酶是一种关键的 TCA 途径成分，可消除饮食选择对寿命的影响。