Science：少食多餐不可取？在对的时间进食七分饱，延寿效果翻倍！

2022-05-15 Swagpp MedSci原创

Science：30%的卡路里限制能够使小鼠寿命延长10%，但是将进食时间限制在小鼠最活跃的时间段，小鼠的寿命能够延长35%。在对的时间吃饭，能使卡路里限制产生的！

现代抗衰老研究的开端可以追溯至上世纪30年代的卡路里限制实验，随后，越来越多的研究证明了卡路里限制能够显著延长线虫、果蝇、小鼠、大鼠等模式动物的寿命，延缓衰老相关疾病的发生，奠定了卡路里限制在抗衰老领域中的主流地位。

但是卡路里限制延长寿命的结论在人类身上是否成立，至今没有答案。科学家试图从人类近亲恒河猴（与人类基因组有93%序列一致性）身上找到证据，证明卡路里限制能够延长灵长类动物寿命。

1980年代，美国国家衰老研究所（NIA）和威斯康星大学分别在恒河猴身上进行了卡路里限制实验。NIA的实验结果显示，卡路里限制对恒河猴生存率没有显著影响；而威斯康星大学的研究则指出卡路里限制能够显著改善恒河猴的健康状态、降低与年龄相关的死亡率和全因死亡率。

图注：同龄的对照组猴子（AB）与卡路里限制组猴子（CD）外形对比

同样是恒河猴实验得到的结论为何大不相同？后来的科学家在对这两项实验进行复盘时，发现了一个小细节——NIA的猴子限制卡路里摄入的基础上，并不限制进食的时间，猴子们在夜间也能够吃到食物；而威斯康星大学的猴子，进食时间被严格限制在8:00-16:00。

进食的时间，可能会对卡路里限制实验结果造成影响。

进行卡路里限制的2型糖尿病患者，在早中午时间吃完一天中大部分食物，比全天分成六餐吃，获得的代谢益处更大。

前一段时间，南方医科大学的张惠杰教授团队发表于NEJM上的一项研究也表明比起单独的卡路里限制，限时进食+卡路里限制在改善肥胖人群的体重、腰围、体脂、血压、空腹血糖等指标方面效果要更好一些（虽然未达到统计学显著性）。

近期，Science上的一项研究更是将卡路里限制、限时进食、生物钟节律相结合，历时四年时间，证明30%的卡路里限制能够使小鼠寿命延长10%，但是将进食时间限制在小鼠最活跃的时间段（小鼠是一种夜间活动的动物），小鼠的寿命能够延长35%，换句话说，在对的时间吃饭，能使卡路里限制产生的延寿效果更上一层楼。

实验小鼠按照是否进行30%的卡路里限制（Caloric restriction, CR），在卡路里限制的基础上是否进行限时进食，以及限时进食时间是否和生物钟节律相符合，分成6组：

对照组：随意进食
全天CR组（CR-spread）：卡路里限制的基础上，食物分配到全天；
白天2小时限时进食CR组（CR-day-2h）：卡路里限制的基础上，将进食时间集中在白天开始后的2小时内；
夜间2小时限时进食CR组（CR-night-2h）：卡路里限制的基础上，将进食时间集中在夜晚开始后的2小时内；
白天12小时限时进食CR组（CR-day-12h）：卡路里限制的基础上，将进食时间集中在白天12小时；
夜间12小时限时进食CR组（CR-night-12h）：卡路里限制的基础上，将进食时间集中在夜间12小时。

研究结果显示：与对照组相比，全天CR组小鼠中位寿命延长了10%；白天2小时或12小时限时进食CR组中位寿命分别延长了21.1%和18.9%；夜间2小时或12小时限时进食CR组中位寿命分别延长了34.8%和33.6%.。

换句话说，单独的卡路里限制，只能延长10%的寿命，而结合了限时进食，延寿效果能增加一倍以上，更进一步，将限时进食的时间限制在小鼠最为活跃的夜间（对应人类是白天），和白天限时进食相比，则又能额外获得将近15%的延寿效益。

在卡路里限制的基础上，配合生物钟节律的限时进食，三管齐下，使得延寿效果最大化。

不仅如此，虽然各组小鼠在生命的晚期大都患上了的疾病，最常见就是组织细胞肉瘤和肝细胞癌，但是进行卡路里限制的小鼠，疾病发病和对照组相比会更晚，意味着卡路里限制的小鼠健康寿命（healthspan）更长，说明卡路里限制不仅延长了生命的长度，还提高了生命的质量。

除了延长寿命，和对照组相比，所有卡路里限制组在血糖代谢方面都表现得更好，卡路里限制的小鼠体内水平始终维持在一个较低状态，提示这些小鼠胰岛素敏感性更高，出现胰岛素抵抗可能性更低，特别是在夜间限时进食的小鼠身上，效果更为明显。

在基因表达方面，衰老引起炎症相关基因表达上升，降低代谢和生物钟节律基因表达，而卡路里限制则能够减轻这种趋势，和随意进食的衰老小鼠相比，进行卡路里限制的小鼠基因表达特征和年轻小鼠更为相似，同样，在夜间限时进食小鼠衰老的基因表达改变最少。

已知多个与延寿相关的代谢分子都受体内生物钟系统的调控，包括insulin、IGF-1、SIRT1、NAMPT、AMPK、PGC-1α等。生物钟、代谢通路及寿命延长之间千丝万缕的联系，也许正是在顺应生物钟节律的情况下进行卡路里限制使延寿效应如虎添翼的原因。

不管怎么说，从研究结果我们可以得出，卡路里限制要想发挥最大的益处，进食时间必须限制在机体活跃的时间段，至于限时进食的时间是2小时还是12小时，效果差别并不是很大。

至少本研究的发起人之一Takahashi就准备从小鼠身上吸取经验——将进食时间限制在12小时内。相信这对大多数人而言，也不难达到。

参考资料

[1]Acosta-Rodríguez V, Rijo-Ferreira F, Izumo M, et al. Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice [published online ahead of print, 2022 May 5]. Science. 2022;. doi:10.1126/science.abk0297

[2]Lee MB, Hill CM, Bitto A, Kaeberlein M. Antiaging diets: Separating fact from fiction. Science. 2021;374(6570):eabe7365. doi:10.1126/science.abe7365

[3]Caloric restriction improves health and survival of rhesus monkeys. Nat Commun. 2017;8:14063. Published 2017 Jan 17. doi:10.1038/ncomms14063

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#插入话题

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2022-05-16 jichang

#SCIE#

64 0
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2022-05-16 gj0737

#进食#

59 0
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2022-05-15 weigq

不能吃夜宵了😭

99 0
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2022-05-15 ms6000000960504356

#学习##心血管#

79 0
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2022-05-15 ms6000000960504356

符合中国人的饮食习惯

73 0
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2022-05-15 ms5000000518166734

学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习

93 0
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2022-05-15 14363817m20暂无昵称

学习

58 0

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