Matching Dietary Amino Acid Balance to the In Silico-Translated Exome Optimizes Growth and Reproduction without Cost to Lifespan

摘要

class="head no_bottom_margin" id="sec1title">IntroductionDiets should ideally match the nutritional needs of their consumers for important life history traits such as growth, reproduction, and lifespan. However, quantifying a balanced diet is challenging given the large numbers of nutrients involved. Among the major macronutrients, the proportion of protein is especially important, since relatively high levels that are important to sustain early life fitness can also incur a heavy cost to lifespan (, ). Thus, establishing protein balance is critical for understanding how diets can be used to enhance lifelong health.Many organisms possess mechanisms to prioritize and maintain protein intake to a narrow range of values that are higher than those optimal for longer-term health (). For example, when protein is relatively low in the diet, total food intake is elevated to maintain protein intake, causing overconsumption of other nutrients (), a situation thought to contribute to obesity. By contrast, when dietary protein content is high, total food consumption is curbed such that energy may be underconsumed—a formulation effectively exploited for weight loss, but also associated with shortened lifespan in insects, mice (, , ), and humans (). Thus, our evolutionary histories drive consumption of imbalanced foods in a manner that is associated with poor long-term health outcomes.Investigations into why these trade-offs exist, and how they might be reduced, form an intense area of research into how dietary restriction (DR) extends healthy lifespan (). A long-held idea, derived from life history theory, is that DR improves lifespan by redirecting limiting resources away from reproduction toward somatic maintenance (, ). However, supplementing the DR diet with methionine (M) in flies can improve reproduction without any cost to lifespan (, ). Thus, enhancing dietary protein quality can increase early life fitness without compromising lifespan. However, understanding how to optimize dietary amino acid (AA) content is not trivial as it represents a 20-dimensional balancing problem. Whereas a theoretical framework is now established (), a quantitative, evidence-based approach to optimal dietary balance design that does not rely on empirical data has so far proved elusive. The discovery of such a definition for major dietary components would be transformative: diets could be designed to match the requirements of the consumer without the need for lengthy trials. Here we report such a theory for dietary AA balance.