NEJM:间歇性禁食对健康、衰老和疾病的影响

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根据Weindruch和Sohal在1997年“期刊”上的一篇文章中所说,减少一生中的食物供应(卡路里限制)对动物的衰老和寿命有显著的影响。作者提出,卡路里限制对健康的好处是被动地减少有害氧自由基的产生。当时,人们还没有普遍认识到,由于限制卡路里的啮齿动物每天的禁食期长达20小时,在此期间会发生酮类生成。


在动物和人类中的研究表明,间歇禁食的许多健康益处不仅仅是减少自由基的产生或减肥的结果。相反,间歇禁食引起进化上保守的适应性细胞反应,这些反应以一种改善葡萄糖调节、提高抗应激能力和抑制信息的方式整合在器官之间和器官内。在禁食期间,细胞激活增强体内防御氧化和代谢压力的途径,以及移除或修复受损分子的途径。


01
间歇性禁食和代谢转换


葡萄糖和脂肪酸是细胞的主要能量来源。在禁食期间,甘油三酸酯分解为脂肪酸和甘油,它们被用作能量。肝脏将脂肪酸转化为酮体,这在禁食期间为许多组织(尤其是大脑)提供了主要能量来源。


02
间歇性禁食和抗压力


反复暴露在禁食环境中会导致持久的适应性反应,从而对随后的挑战产生抵抗力。细胞对间歇性禁食的反应是通过参与协调的适应性应激反应,导致抗氧化防御、dna修复、蛋白质质量控制、有丝分裂生物发生和自噬的表达增加,以及炎症的下调。


03
间歇性禁食对健康和衰老的影响


在对动物热量限制进行了近一个世纪的研究后,总体结论是减少食物摄入量可以有效地延长寿命。

在人类中,间歇性禁食可以减轻肥胖,胰岛素抵抗,血脂异常,高血压和炎症。


04
间歇性禁食的身体和认知作用


动物研究表明,间歇性禁食可增强多个领域的认知,包括空间记忆,联想记忆和工作记忆。隔日禁食和每日热量限制可以逆转肥胖,糖尿病和神经炎症对空间学习和记忆的不利影响


原文阅读


According to Weindruch and Sohal in a 1997 article in the Journal, reducing  food  availability  over  a  lifetime  (caloric  restriction)  has  remarkable effects on aging and the life span in animals.1 The authors proposed that the health benefits of caloric restriction result from a passive reduction in the production  of  damaging  oxygen  free  radicals.  At  the  time,  it  was  not  generally  recognized  that  because  rodents  on  caloric  restriction  typically  consume  their  entire  daily  food  allotment  within  a  few  hours  after  its  provision,  they  have  a  daily  fasting  period  of  up  to  20  hours,  during  which  ketogenesis  occurs.  Since  then, hundreds of studies in animals and scores of clinical studies of controlled intermittent fasting regimens have been conducted in which metabolic switching from liver-derived glucose to adipose cell–derived ketones occurs daily or several days each week. Although the magnitude of the effect of intermittent fasting on life-span extension is variable (inf luenced by sex, diet, and genetic factors), studies in mice and nonhuman primates show consistent effects of caloric restriction on the health span Studies in animals and humans have shown that many of the health benefits of intermittent fasting are not simply the result of reduced free-radical production or  weight  loss.2-5  Instead,  intermittent  fasting  elicits  evolutionarily  conserved,  adaptive  cellular  responses  that  are  integrated  between  and  within  organs  in  a  manner  that  improves  glucose  regulation,  increases  stress  resistance,  and  sup-presses inf lammation. During fasting, cells activate pathways that enhance intrin-sic defenses against oxidative and metabolic stress and those that remove or repair damaged  molecules 


Intermittent  Fasting and Metabolic Switching

Glucose and fatty acids are the main sources of energy for cells. After meals, glucose is used for energy,  and  fat  is  stored  in  adipose  tissue  as  triglycerides. During periods of fasting, triglyc-erides are broken down to fatty acids and glycerol,  which  are  used  for  energy.  The  liver  con-verts fatty acids to ketone bodies, which provide a major source of energy for many tissues, espe-cially  the  brain,  during  fasting 


Intermittent Fasting and Stress Resistance

Repeated exposure to fasting periods  results  in  lasting  adaptive  responses  that  confer resistance to subsequent challenges. Cells respond to intermittent fasting by engaging in a coordinated  adaptive  stress  response  that  leads  to increased expression of antioxidant defenses, DNA  repair,  protein  quality  control,  mitochondrial biogenesis and autophagy, and down-regulation  of  inflammation


Effects of Intermittent Fasting on Health and Aging

After  nearly  a  century  of  research  on  caloric restriction in animals, the overall conclusion  was  that  reduced  food  intake  robustly  in-creases the life span. In humans, intermittent-fasting interventions ameliorate obesity, insulin resistance, dyslipid-emia, hypertension, and inf lammation.


Physical and Cognitive Effects of Intermittent Fasting

Studies  in  animals  show  that  intermittent  fasting enhances cognition in multiple domains, including  spatial  memory,  associative  memory,  and working memory; alternate-day fasting and daily caloric restriction reverse the adverse effects of obesity, diabetes, and neuroinf lammation on spatial learning and memory


Reference:

Effects of Intermittent Fasting on Health, Aging, and Disease. N Engl J Med 2019;381:2541-51.




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