van Norren Klaske, Rusli Fenni, van Dijk Miriam, Lute Carolien, Nagel Jolanda, Dijk Francina J, Dwarkasing Jvalini, Boekschoten Mark V, Luiking Yvette, Witkamp Renger F, Müller Michael, Steegenga Wilma T
Nutrition and Pharmacology Group, Division of Human Nutrition, Wageningen University Wageningen, The Netherlands ; Nutricia Research Utrecht, The Netherlands.
Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University Wageningen, The Netherlands.
J Cachexia Sarcopenia Muscle. 2015 Sep;6(3):253-68. doi: 10.1002/jcsm.12024. Epub 2015 Apr 27.
In rodent models, caloric restriction (CR) with maintenance of adequate micronutrient supply has been reported to increase lifespan and to reduce age-induced muscle loss (sarcopenia) during ageing. In the present study, we further investigated effects of CR on the onset and severity of sarcopenia in ageing male C57BL/6 J mice. The aim of this study was to investigate whether CR induces changes in behaviour of the animals that could contribute to the pronounced health-promoting effects of CR in rodents. In addition, we aimed to investigate in more detail the effects of CR on the onset and severity of sarcopenia.
The mice received either an ad libitum diet (control) or a diet matching 70 E% of the control diet (C). Daily activity, body composition (dual energy X-ray absorptiometry), grip strength, insulin sensitivity, and general agility and balance were determined at different ages. Mice were killed at 4, 12, 24, and 28 months. Skeletal muscles of the hind limb were dissected, and the muscle extensor digitorum longus muscle was used for force-frequency measurements. The musculus tibialis was used for real-time quantitative PCR analysis.
From the age of 12 months, CR animals were nearly half the weight of the control animals, which was mainly related to a lower fat mass. In the control group, the hind limb muscles showed a decline in mass at 24 or 28 months of age, which was not present in the CR group. Moreover, insulin sensitivity (oral glucose tolerance test) was higher in this group and the in vivo and ex vivo grip strength did not differ between the two groups. In the hours before food was provided, CR animals were far more active than control animals, while total daily activity was not increased. Moreover, agility test indicated that CR animals were better climbers and showed more climbing behaviours.
Our study confirms earlier findings that in CR animals less sarcopenia is present. The mice on the CR diet, however, showed specific behavioural changes characterized by higher bursts of activity within a short time frame before consumption of a 70 E% daily meal. We hypothesize that the positive effects of CR on muscle maintenance in rodents are not merely a direct consequence of a lower energy intake but also related to a more active behaviour in a specific time frame. The burst of activity just before immediate start of eating, might lead to a highly effective use of the restricted protein sources available.
在啮齿动物模型中，有报道称在维持充足微量营养素供应的情况下进行热量限制（CR）可延长寿命，并减少衰老过程中年龄诱导的肌肉损失（肌肉减少症）。在本研究中，我们进一步研究了CR对衰老雄性C57BL / 6 J小鼠肌肉减少症的发病和严重程度的影响。本研究的目的是调查CR是否会引起动物行为的变化，这些变化可能有助于解释CR在啮齿动物中显著的健康促进作用。此外，我们旨在更详细地研究CR对肌肉减少症发病和严重程度的影响。
小鼠分别接受自由采食饮食（对照组）或摄入相当于对照组饮食70 E%的饮食（CR组）。在不同年龄测定每日活动量、身体成分（双能X线吸收法）、握力、胰岛素敏感性以及一般敏捷性和平衡能力。在4、12、24和28个月时处死小鼠。解剖后肢的骨骼肌，使用趾长伸肌进行力-频率测量。使用胫肌进行实时定量PCR分析。
从12个月龄开始，CR组动物的体重几乎是对照组动物的一半，这主要与较低的脂肪量有关。在对照组中，后肢肌肉在24或28个月龄时出现质量下降，而CR组未出现这种情况。此外，该组的胰岛素敏感性（口服葡萄糖耐量试验）较高，两组的体内和体外握力没有差异。在提供食物前的几个小时，CR组动物比对照组动物活跃得多，而每日总活动量并未增加。此外，敏捷性测试表明CR组动物攀爬能力更强，表现出更多的攀爬行为。
我们的研究证实了早期的发现，即CR组动物的肌肉减少症较少。然而，采用CR饮食的小鼠表现出特定的行为变化，其特征是在每日进食70 E%食物之前的短时间内活动爆发性增加。我们推测，CR对啮齿动物肌肉维持的积极作用不仅是能量摄入降低的直接结果，还与特定时间框架内更活跃的行为有关。就在进食开始前的活动爆发，可能会导致对可用的受限蛋白质来源的高效利用。
