Hou Chen, Bolt Kendra, Bergman Aviv
Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
BMC Syst Biol. 2011 May 19;5:78. doi: 10.1186/1752-0509-5-78.
Caloric restriction (CR) has been shown to keep organisms in a relatively youthful and healthy state compared to ad libitum fed counterparts, as well as to extend the lifespan of a diverse set of organisms. Several attempts have been made to understand the underlying mechanisms from the viewpoint of energy tradeoffs in organisms' life histories. However, most models are based on assumptions which are difficult to justify, or are endowed with free-adjusting parameters whose biological relevancy is unclear.
In this paper, we derive a general quantitative, predictive model based on physiological data for endotherms. We test the hypothesis that an animal's state of health is correlated with biological mechanisms responsible for the maintenance of that animal's functional integrities. Such mechanisms require energy. By suppressing animals' caloric energy supply and biomass synthesis, CR alters animals' energy allocation strategies and channels additional energy to those maintenance mechanisms, therefore enhancing their performance. Our model corroborates the observation that CR's effects on health maintenance are positively correlated with the degree and duration of CR. Furthermore, our model shows that CR's effects on health maintenance are negatively correlated to the temperature drop observed in endothermic animals, and is positively correlated to animals' body masses. These predictions can be tested by further experimental research.
Our model reveals how animals will alter their energy budget when food availability is low, and offers better understanding of the tradeoffs between growth and somatic maintenance; therefore shedding new light on aging research from an energetic viewpoint.
与自由采食的同类生物相比，热量限制（CR）已被证明能使生物保持相对年轻和健康的状态，还能延长多种生物的寿命。人们已多次尝试从生物生命历程中的能量权衡角度来理解其潜在机制。然而，大多数模型基于难以论证的假设，或带有生物相关性不明的自由调整参数。
在本文中，我们基于恒温动物的生理数据推导了一个通用的定量预测模型。我们检验了这样一个假设：动物的健康状态与负责维持该动物功能完整性的生物机制相关。此类机制需要能量。通过抑制动物的热量能量供应和生物量合成，热量限制改变了动物的能量分配策略，并将额外的能量导向那些维持机制，从而提高其性能。我们的模型证实了以下观察结果：热量限制对健康维持的影响与热量限制的程度和持续时间呈正相关。此外，我们的模型表明，热量限制对健康维持的影响与恒温动物中观察到的体温下降呈负相关，与动物体重呈正相关。这些预测可通过进一步的实验研究进行检验。
我们的模型揭示了食物供应不足时动物将如何改变其能量预算，并有助于更好地理解生长与躯体维持之间的权衡；因此从能量角度为衰老研究提供了新的视角。
