Wheatley William S R, Marshall Christopher J, Taddei Ludovico, Hitrec Timna, Pickering Anthony E, Ambler Michael T
School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, BS8 1TD, UK.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, 40127, Italy.
J Comp Physiol B. 2025 Jun 9. doi: 10.1007/s00360-025-01616-1.
Calorie restriction has been shown to dramatically extend lifespan in a range of species. Beyond longevity, calorie restriction is also reported to improve cognitive function, ameliorate neurodegeneration and peripheral nerve damage, reduce cancer incidence, and is commonly used to increase motivation in studies of behaviour. The mouse has been the most common species for these experiments and whilst efforts are ongoing to demonstrate the benefits of calorie restriction in humans, the evidence in mice is most compelling. Many mechanisms have been proposed for the beneficial effects of calorie restriction, but we note that one potentially important factor has seldom been considered: namely that mice readily enter torpor in response to food restriction. Torpor is a remarkable protective physiological state characterized by profound reductions in body temperature, oxygen consumption, heart rate, and activity. In this review, we describe the dietary protocols used to study the effects of calorie restriction and present the case that mice in these studies are highly likely to have entered torpor. We discuss the extent to which torpor might influence or mediate the measured outcomes. We highlight that induction of torpor is an important confound that is rarely, if at all, considered in calorie restriction research and make recommendations for the design and conduct of future studies.
热量限制已被证明能显著延长一系列物种的寿命。除了延长寿命外，热量限制还被报道能改善认知功能、减轻神经退行性变和周围神经损伤、降低癌症发病率，并且在行为研究中通常被用于提高动机。小鼠一直是这些实验中最常用的物种，虽然目前正在努力证明热量限制对人类的益处，但小鼠身上的证据最有说服力。关于热量限制的有益作用，人们提出了许多机制，但我们注意到一个潜在的重要因素很少被考虑：即小鼠很容易因食物限制而进入蛰伏状态。蛰伏是一种显著的保护性生理状态，其特征是体温、耗氧量、心率和活动大幅降低。在这篇综述中，我们描述了用于研究热量限制影响的饮食方案，并指出在这些研究中的小鼠很可能进入了蛰伏状态。我们讨论了蛰伏可能影响或介导测量结果的程度。我们强调，蛰伏的诱导是热量限制研究中一个重要的混杂因素，即使有考虑也很少，同时我们为未来研究的设计和开展提出建议。
