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

在没有营养不良的情况下，能量限制（ER）已经被认为可以延缓各种哺乳动物的衰老过程和延长寿命。本研究以秋田犬为食，研究内质网对C57Bl/6雄性小鼠心脏基因表达及生理特性的影响。我们利用覆盖6400个基因的cDNA芯片分析了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mrna升高，153个基因mrna降低。提示内质网心脏的微观结构和电生理特性可能会发生改变，以适应低能量和低温。老龄小鼠的长期动态体温和心电图记录显示，ER小鼠心率的上下变化先于体温的上下变化（即观察到迟滞）。这意味着ER心脏在改变体温方面起着重要作用。当体温下降时，心率急剧下降到五分之一，在ER小鼠中观察到室性上心律失常，就像在冬眠动物中一样。ER对心电图波形无明显影响。心率变异性分析显示，ER组的副交感神经活动高于Ct组。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。综上所述，内质网可能改变心脏的结构和功能特性，使其适应大范围的体温和能量供应。这也表明，抗心律失常适应可能发生在ER小鼠的心脏，这可能有助于延长它们的寿命。

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.