Hambly Catherine, Mercer Julian G, Speakman John R
Aberdeen Centre for Energy Regulation and Obesity (ACERO), Rowett Research Institute, Bucksburn, Aberdeen, Scotland, United Kingdom.
Rejuvenation Res. 2007 Dec;10(4):533-42. doi: 10.1089/rej.2007.0555.
Caloric restriction (CR) is the only nongenetic manipulation known to reliably prolong life-span. Modeling suggests that humans would need to restrict their intake for many years to reap any lifespan benefits. The feasibility of such prolonged restriction may hinge on whether hunger diminishes with the time period spent restricted. We used the magnitude of hyperphagia on release from restriction as a bioassay of hunger in restricted mice. During restriction, mice develop a characteristic pattern of neuropeptide signals in the arcuate nucleus that reflect their hunger. This pattern is normalized after the postrestriction hyperphagia, validating hyperphagia as an indicator of the hunger during restriction. Mice were food restricted (80% of ad lib.) for 50 days. They initially lost weight, but then became weight stable and were maintained in CR at this lower level of energy balance for between 0 and 50 days and were then fed ad lib. for 50 days. When released onto ad lib. food, the magnitude of the hyperphagic response was independent of the prior length of CR. Hyperphagia ended when body mass was normalized. Hunger therefore did not diminish even when they were restricted for 100 days, equivalent to about 11 years in humans. The pattern of hyperphagic response suggested that signals coding body mass drive hunger during restriction, and because body mass under restriction remains depressed, this suggests that hunger would never disappear, making restriction to prolong lifespan in humans difficult to accomplish.
热量限制（CR）是已知的唯一能可靠延长寿命的非基因干预手段。模型显示，人类需要多年限制热量摄入才能获得寿命延长的益处。这种长期限制的可行性可能取决于饥饿感是否会随着限制时间的延长而减轻。我们将限制解除后过度摄食的程度作为受限小鼠饥饿程度的生物测定指标。在限制期间，小鼠在弓状核中形成一种特征性的神经肽信号模式，反映它们的饥饿程度。在限制后的过度摄食后，这种模式恢复正常，这证实了过度摄食是限制期间饥饿的一个指标。小鼠被限制食物摄入量（自由摄食量的80%）50天。它们最初体重下降，但随后体重稳定，并在这种较低能量平衡水平下维持热量限制0至50天，然后自由进食50天。当恢复自由进食时，过度摄食反应的程度与之前热量限制的时长无关。当体重恢复正常时，过度摄食结束。因此，即使小鼠被限制100天（相当于人类约11年），饥饿感也不会减轻。过度摄食反应模式表明，编码体重的信号在限制期间驱动饥饿感，而且由于限制期间体重持续下降，这表明饥饿感永远不会消失，使得通过限制热量摄入来延长人类寿命难以实现。
