{"title":"热量限制调节的分子途径及其对不同年龄组的影响:综述。","authors":"Anuradha Rachakatla, Rajender Rao Kalashikam","doi":"10.1089/dna.2021.0922","DOIUrl":null,"url":null,"abstract":"Calorie restriction (CR) if planned properly with regular exercise at different ages can result in healthy weight loss. CR can also have different beneficial effects on improving lifespan and decreasing the age-associated diseases by regulating physiological, biochemical, and molecular markers. The different pathways regulated by CR include:(1) AMP-activated protein kinase (AMPK), which involves PGC-1α, SIRT1, and SIRT3. AMPK also effects myocyte enhancer factor 2 (MEF2), peroxisome proliferator-activated receptor delta, and peroxisome proliferator-activated receptor alpha, which are involved in mitochondrial biogenesis and lipid oxidation; (2) Forkhead box transcription factor's signaling is related to the DNA repair, lipid metabolism, protection of protein structure, autophagy, and resistance to oxidative stress; (3) Mammalian target of rapamycin (mTOR) signaling, which involves key factors, such as S6 protein kinase-1 (S6K1), mTOR complex-1 (mTORC1), and 4E-binding protein (4E-BP). Under CR conditions, AMPK activation and mTOR inhibition helps in the activation of Ulk1 complex along with the acetyltransferase Mec-17, which is necessary for autophagy; (4) Insulin-like growth factor-1 (IGF-1) pathway downregulation protects against cancer and slows the aging process; (5) Nuclear factor kappa B pathway downregulation decreases the inflammation; and (6) c-Jun N-terminal kinase and p38 kinase regulation as a response to the stress. The acute and chronic CR both shows antidepression and anxiolytic action by effecting ghrelin/GHS-R1a signaling. CR also regulates GSK3β kinase and protects against age-related brain atrophy. CR at young age may show many deleterious effects by effecting different mechanisms. Parental CR before or during conception will also affect the health and development of the offspring by causing many epigenetic modifications that show transgenerational transmission. Maternal CR is associated with intrauterine growth retardation effecting the offspring in their adulthood by developing different metabolic syndromes. The epigenetic changes with response to paternal food supply also linked to offspring health. 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The different pathways regulated by CR include:(1) AMP-activated protein kinase (AMPK), which involves PGC-1α, SIRT1, and SIRT3. AMPK also effects myocyte enhancer factor 2 (MEF2), peroxisome proliferator-activated receptor delta, and peroxisome proliferator-activated receptor alpha, which are involved in mitochondrial biogenesis and lipid oxidation; (2) Forkhead box transcription factor's signaling is related to the DNA repair, lipid metabolism, protection of protein structure, autophagy, and resistance to oxidative stress; (3) Mammalian target of rapamycin (mTOR) signaling, which involves key factors, such as S6 protein kinase-1 (S6K1), mTOR complex-1 (mTORC1), and 4E-binding protein (4E-BP). 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引用次数: 2
摘要
如果在不同的年龄进行适当的计划和有规律的运动,热量限制(CR)可以达到健康的减肥效果。CR还可以通过调节生理、生化和分子标记,对延长寿命和减少与年龄相关的疾病产生不同的有益影响。CR调节的不同途径包括:(1)amp活化蛋白激酶(AMPK),涉及PGC-1α、SIRT1和SIRT3。AMPK还影响心肌细胞增强因子2 (MEF2)、过氧化物酶体增殖物激活受体δ和过氧化物酶体增殖物激活受体α,它们参与线粒体生物发生和脂质氧化;(2)叉头盒转录因子的信号转导与DNA修复、脂质代谢、蛋白质结构保护、自噬、抗氧化应激等有关;(3)哺乳动物雷帕霉素(mTOR)信号通路靶点,涉及S6蛋白激酶-1 (S6K1)、mTOR复合物-1 (mTORC1)、4e结合蛋白(4E-BP)等关键因子。在CR条件下,AMPK激活和mTOR抑制有助于Ulk1复合物和乙酰转移酶Mec-17的激活,这是自噬所必需的;(4)胰岛素样生长因子-1 (IGF-1)通路下调具有抗癌和延缓衰老作用;(5)核因子κ B通路下调可减轻炎症反应;(6) c-Jun n -末端激酶和p38激酶的调控对胁迫的响应。急性和慢性CR均通过影响ghrelin/GHS-R1a信号通路表现出抗抑郁和抗焦虑作用。CR还调节GSK3β激酶,并防止与年龄相关的脑萎缩。幼年期CR可能通过不同的机制表现出许多有害的影响。父母在受孕前或怀孕期间的CR也会影响后代的健康和发育,导致许多表现为跨代遗传的表观遗传修饰。母体CR与宫内生长迟缓有关,通过发展不同的代谢综合征影响后代成年期。表观遗传变化对父亲食物供应的反应也与后代健康有关。中老年CR对老年相关疾病的发展具有重要的预防作用。
Calorie Restriction-Regulated Molecular Pathways and Its Impact on Various Age Groups: An Overview.
Calorie restriction (CR) if planned properly with regular exercise at different ages can result in healthy weight loss. CR can also have different beneficial effects on improving lifespan and decreasing the age-associated diseases by regulating physiological, biochemical, and molecular markers. The different pathways regulated by CR include:(1) AMP-activated protein kinase (AMPK), which involves PGC-1α, SIRT1, and SIRT3. AMPK also effects myocyte enhancer factor 2 (MEF2), peroxisome proliferator-activated receptor delta, and peroxisome proliferator-activated receptor alpha, which are involved in mitochondrial biogenesis and lipid oxidation; (2) Forkhead box transcription factor's signaling is related to the DNA repair, lipid metabolism, protection of protein structure, autophagy, and resistance to oxidative stress; (3) Mammalian target of rapamycin (mTOR) signaling, which involves key factors, such as S6 protein kinase-1 (S6K1), mTOR complex-1 (mTORC1), and 4E-binding protein (4E-BP). Under CR conditions, AMPK activation and mTOR inhibition helps in the activation of Ulk1 complex along with the acetyltransferase Mec-17, which is necessary for autophagy; (4) Insulin-like growth factor-1 (IGF-1) pathway downregulation protects against cancer and slows the aging process; (5) Nuclear factor kappa B pathway downregulation decreases the inflammation; and (6) c-Jun N-terminal kinase and p38 kinase regulation as a response to the stress. The acute and chronic CR both shows antidepression and anxiolytic action by effecting ghrelin/GHS-R1a signaling. CR also regulates GSK3β kinase and protects against age-related brain atrophy. CR at young age may show many deleterious effects by effecting different mechanisms. Parental CR before or during conception will also affect the health and development of the offspring by causing many epigenetic modifications that show transgenerational transmission. Maternal CR is associated with intrauterine growth retardation effecting the offspring in their adulthood by developing different metabolic syndromes. The epigenetic changes with response to paternal food supply also linked to offspring health. CR at middle and old age provides a significant preventive impact against the development of age-associated diseases.
期刊介绍:
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