Cell子刊:饥饿或是热量限制饮食延长寿命的关键因素

2022-05-22 生物世界 生物世界

实验结果表明,经历饥饿的过程或是热量限制延长寿命和延长健康寿命背后机制的关键因素之一。 

热量限制(Caloric Restriction,CR)是指在充分保证生物体营养成分(如必需氨基酸、维生素和各种微量元素)的情况下限制生物体每天只摄入少量有限的能量,是目前在多种模式动物中验证过的最有效的改善健康状况延长寿命的方法之一,但背后具体生物学机制尚不明确。

热量限制是人为限制动物的食物摄取量,传统的实施方法是:假设平时每天摄入10g食物,进行30%的能量限制,那么每天只提供7g。然而,这种方法对于果蝇和秀丽线虫等模式生物不适用,因而在这些动物中使用了替代原始CR的限制方法热量稀释(Calorie Dilution,CD)——在食物中添加水或不能被动物分解吸收的物质如纤维素(肠道中不含纤维素酶因此能量无法被分解吸收)来稀释单位食物热量,进而造成一定热量限制。

然而,当使用添加纤维素的食物在小鼠上进行热量限制实验时,受试动物的增寿现象消失了。

中国科学院遗传与发育生物学研究所/深圳先进技术研究院 John R. Speakman 研究组在 Cell 子刊 Cell Reports 上发表了题为:Calorie restriction and calorie dilution have different impacts on body fat, metabolism, behavior and hypothalamic gene expression 的研究论文。

该研究探究了这两种不同的“限制”热量方法对模式动物的不同影响。研究分别采用传统热量限制方法CR和纤维素稀释食物的方法CD,对C57BL/6系小鼠进行90天的热量限制,观察并比较了在能量限制期间两种限制方法下小鼠的体重、脂肪重量、各个器官组织应对能量匮乏的响应、代谢生理指标、动物行为的差异以及在能量限制后两组小鼠下丘脑的基因表达谱的差异及与对照组的差异。

实验结果表明,经历饥饿的过程或是热量限制延长寿命和延长健康寿命背后机制的关键因素之一。 

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实验中,研究对CD组小鼠饲喂含有50%纤维素的食物,CR组小鼠被投喂与CD组相同热量的普通正常食物。相对于正常饮食的小鼠,两种不同模式的CR小鼠体重均出现了快速明显下降,具体表现为体重下降和体内脂肪含量的降低,相比传统意义的CR来说,CD小鼠脂肪质量下降更为显著(图1) 。

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图1:两种形式CR下,小鼠体重和体内脂肪含量的改变 

在相关激素方面,两种模式的CR小鼠均出现了Leptin(瘦素)和胰岛素的显著下降。在能量代谢方面,它们都出现了代谢率的下降,而CR小鼠下降得更为明显。两种热量限制方法对动物行为产生的影响差异也较大。CR小鼠在每天投喂食物前会表现出明显的食物预期行为;而CD小鼠则在白天更加活跃(图2)。  

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图2:CR小鼠相比于CD小鼠表现出更强的食物预期行为

研究团队利用RNA-Seq进一步对两组限制组及对照组小鼠的下丘脑基因表达谱进行分析研究,对比两种不同模式的CR发现,两者主要的区别在于小鼠在饥饿状态下一些与饥饿通路相关的基因表达改变,如下调酪氨酸羟化酶D5受体(多巴胺受体)的基因表达。

CR和CD组之间未发现相关神经肽表达的差异,两组相对于CT组,它们均显示出促食欲神经肽NPY和AgRP的基因表达增加,且POMC和CART的水平降低。

然而,研究发现,两者存在相对细小的差异,16个基因在CR里相对于CD上调,同时另有16个基因相对下调。而CR相对于CD的上调基因里包括许多在饥饿时表达会增强的基因如Hif3、Tsc22d3、pdk4、fmo2等(图3)。结果表明,尽管摄入相同热量,CR小鼠确实比CD小鼠更饿。该基因表达谱的结果与之前观察到的它们的动物行为相符合。 

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图3:饥饿信号通路图。CD组相对CR组,蓝色表示下调基因,红色表示上调基因

该研究发现小鼠在摄入相同热量的条件下,使用不同的限制方式,即CR——饿肚子(存在长时间饥饿不进食的过程)以及CD——一直不停吃(没有饥饿的过程),会产生完全不同的生理表现和基因表达,这揭示了饥饿介导的一系列相关基因表达的改变在热量限制延长寿命方面的重要作用,并为进一步完善CR机制提出了潜在方向。 

论文链接

https://doi.org/10.1016/j.celrep.2022.110835

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    2022-10-13 维他命
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    2022-05-24 心医者

    所以说,饥饿增加寿命,而代餐(没有饥饿过程)不能增加?(但是同时能减脂、减重)

    0

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  5. [GetPortalCommentsPageByObjectIdResponse(id=1872429, encodeId=ad6618e242917, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Mar 18 09:55:07 CST 2023, time=2023-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962755, encodeId=a5641962e5568, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Thu Oct 13 00:55:07 CST 2022, time=2022-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1221951, encodeId=fa98122195183, content=所以说,饥饿增加寿命,而代餐(没有饥饿过程)不能增加?(但是同时能减脂、减重), beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTI2bUaEW9seQrS89Hf7J4kQzdPHyp5hBKbrj6FAia5KHkKfk657m47rt80EZtMk2LPwTyuv0rTR9gQ/132, createdBy=cced2543886, createdName=心医者, createdTime=Tue May 24 10:38:37 CST 2022, time=2022-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1336937, encodeId=149a133693efb, content=<a href='/topic/show?id=91386e25889' target=_blank style='color:#2F92EE;'>#热量限制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67258, encryptionId=91386e25889, topicName=热量限制)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/L2dMhrxjvSWuPWKZZP1I83Rw21EWia7LVTYJibLQkb4oTibrYLwhnAXntTBWR3FruIzKfNMiaBwhYV0AKNmiaNxfialg/132, createdBy=6ea92500119, createdName=ms9608593228839890, createdTime=Tue May 24 00:55:07 CST 2022, time=2022-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1454769, encodeId=6a191454e69db, content=<a href='/topic/show?id=d370101185d7' target=_blank style='color:#2F92EE;'>#饥饿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101185, encryptionId=d370101185d7, topicName=饥饿)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5c9a5593064, createdName=guojianrong, createdTime=Tue May 24 00:55:07 CST 2022, time=2022-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1479906, encodeId=d4b814e9906cf, content=<a href='/topic/show?id=456b4954350' target=_blank style='color:#2F92EE;'>#延长寿命#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49543, encryptionId=456b4954350, topicName=延长寿命)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d9587588723, createdName=hittouch, createdTime=Tue May 24 00:55:07 CST 2022, time=2022-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1613881, encodeId=acd4161388148, content=<a href='/topic/show?id=d87e6e25687' target=_blank style='color:#2F92EE;'>#热量#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67256, encryptionId=d87e6e25687, topicName=热量)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bba919440409, createdName=ms2536978994064944, createdTime=Tue May 24 00:55:07 CST 2022, time=2022-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1221758, encodeId=fdde1221e5881, content=厉害, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220625/6f4f075937de4c5d9fc7ab3a1bc6d8c2/13a8a29e67044698af1fb74276589093.jpg, createdBy=b5c55099112, createdName=D-House, createdTime=Mon May 23 14:55:04 CST 2022, time=2022-05-23, status=1, ipAttribution=)]
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  7. [GetPortalCommentsPageByObjectIdResponse(id=1872429, encodeId=ad6618e242917, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Mar 18 09:55:07 CST 2023, time=2023-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962755, encodeId=a5641962e5568, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Thu Oct 13 00:55:07 CST 2022, time=2022-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1221951, encodeId=fa98122195183, content=所以说,饥饿增加寿命,而代餐(没有饥饿过程)不能增加?(但是同时能减脂、减重), beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTI2bUaEW9seQrS89Hf7J4kQzdPHyp5hBKbrj6FAia5KHkKfk657m47rt80EZtMk2LPwTyuv0rTR9gQ/132, createdBy=cced2543886, createdName=心医者, createdTime=Tue May 24 10:38:37 CST 2022, time=2022-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1336937, encodeId=149a133693efb, content=<a href='/topic/show?id=91386e25889' target=_blank style='color:#2F92EE;'>#热量限制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67258, encryptionId=91386e25889, topicName=热量限制)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/L2dMhrxjvSWuPWKZZP1I83Rw21EWia7LVTYJibLQkb4oTibrYLwhnAXntTBWR3FruIzKfNMiaBwhYV0AKNmiaNxfialg/132, createdBy=6ea92500119, createdName=ms9608593228839890, createdTime=Tue May 24 00:55:07 CST 2022, time=2022-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1454769, encodeId=6a191454e69db, content=<a href='/topic/show?id=d370101185d7' target=_blank style='color:#2F92EE;'>#饥饿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101185, encryptionId=d370101185d7, topicName=饥饿)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5c9a5593064, createdName=guojianrong, createdTime=Tue May 24 00:55:07 CST 2022, time=2022-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1479906, encodeId=d4b814e9906cf, content=<a href='/topic/show?id=456b4954350' target=_blank style='color:#2F92EE;'>#延长寿命#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49543, encryptionId=456b4954350, topicName=延长寿命)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d9587588723, createdName=hittouch, createdTime=Tue May 24 00:55:07 CST 2022, time=2022-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1613881, encodeId=acd4161388148, content=<a href='/topic/show?id=d87e6e25687' target=_blank style='color:#2F92EE;'>#热量#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67256, encryptionId=d87e6e25687, topicName=热量)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bba919440409, createdName=ms2536978994064944, createdTime=Tue May 24 00:55:07 CST 2022, time=2022-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1221758, encodeId=fdde1221e5881, content=厉害, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220625/6f4f075937de4c5d9fc7ab3a1bc6d8c2/13a8a29e67044698af1fb74276589093.jpg, createdBy=b5c55099112, createdName=D-House, createdTime=Mon May 23 14:55:04 CST 2022, time=2022-05-23, status=1, ipAttribution=)]
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    2022-05-23 D-House

    厉害

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