Cold-resistant and anti-arrhythmic adaptation of the heart in mice under energy restriction, and prolongation of their life span

在各种哺乳动物中，没有营养不良的能量限制（ER）可以延缓衰老过程并延长寿命。我们研究了ER对使用秋田饮食的C57 B1/6雄性小鼠心脏的基因表达和生理特性的影响。我们使用覆盖6400个基因的cDNA微阵列分析了ER（200 kJ/周）或对照（Ct）（400 kJ/周）B6 7月龄雄性小鼠心脏mRNA的表达。ER使67个基因的mRNA表达增加，153个基因的mRNA表达降低。对老年小鼠的动态体温和心电图的长期记录表明，ER小鼠心率的变化先于体温的变化（即滞后现象）。这意味着ER心脏在改变体温方面具有重要作用。当体温下降时，心率急剧下降至五分之一，并且在ER小鼠中观察到室上性心律失常，就像在冬眠动物中一样。ER不改变心电图波形。心率变异性的分析表明，副交感神经活性高于在ER比Ct小鼠。随着年龄的增长，ER小鼠的昼夜节律变得与Ct小鼠一样模糊，因此，ER可能改变心脏的结构和功能特性，使其适应更宽的体温和能量利用范围。这也表明ER小鼠心脏可能发生抗心律失常适应，这可能有助于延长其寿命。

Energy restriction (ER) without malnutrition has been known to retard aging processes and extend the life span in various species of mammals. We investigated the effects of ER on gene expression and physiological properties of the heart of C57Bl/6 male mice using AKITA diet. We analyzed the expression of heart mRNA from ER (200 kJ/week) or control (Ct) (400 kJ/week) B6 7-month-old male mice using cDNA microarray covering 6400 genes. mRNAs of 67 genes were increased and those of 153 genes were decreased by ER. It is suggested that the micro-structure and electro-physiological properties of the ER heart may change to adapt low energy and low temperature.Ambulatory long-term recording of body temperature and electrocardiogram of aged mice revealed that the heart rate of ER mice changed up and down before body temperature did (i.e. hysteresis was observed). It means that the ER heart has an important role in changing body temperature. When body temperature decreased, the heart rate was dramatically decreased to one fifth and supra-ventricular arrhythmia was observed in ER mice, as in hibernators. ER did not change shapes of ECG waves. Analysis of heart rate variability revealed that parasympathetic activity was higher in ER than Ct mice. As aged, circadian rhythm of ER mice became obscure as Ct mice.In conclusion, ER may alter structure and functional properties of the heart and make it adaptable to wide range of body temperature and energy availability. This also suggests that anti-arhythmic adaptation may occur in the heart of ER mice, which may contribute to the prolongation of their life span.