 甘氨酸是结构最简单的稳定氨基酸。1820年，法国化学家Henri Braconnot用硫酸水解明胶时首次发现这种“有点甜”的物质，并将其称为“明胶糖”[1]。 时间的齿轮滚滚向前，人们对甘氨酸的认识愈加深入。2021年，一项临床试验发现甘氨酸与搭档NAC（N-乙酰半胱氨酸）联用24周竟能使人“返老还童”：使74岁老人的肌肉力量和身体机能大幅改善、体脂降低4%、腰围缩小4cm，连认知功能也大幅提升，直逼24岁年轻人水平[2]。 随着如此惊人的抗衰数据出炉，甘氨酸迅速为众多专家关注，其中就包括大名鼎鼎的哈佛医学院教授大卫·辛克莱。 最近，他参与创办的抗衰老生物技术公司Tally Health于权威期刊发表综述，肯定甘氨酸的延寿功效，并探究了其延寿的根本原因[3]。  （除综述内容外，本文末有会员群朋友们的甘氨酸服用相关问题解答，不要错过）  许多研究表明，限制蛋氨酸可延寿[4-6]。而本篇综述揭示，补充甘氨酸就可达到限制蛋氨酸效果。 甘氨酸与蛋氨酸之间的联系来自于这样一个有趣的生化反应：在甘氨酸N-甲基转移酶（GNMT）的催化下，甘氨酸从S-腺苷-L-甲硫氨酸（SAM）中获取一个甲基，转变为肌氨酸。   图注：甘氨酸、肌氨酸化学式 这种“夺取甲基”的过程使体内SAM水平下降，阻断了其转变为蛋氨酸的过程，也因此，补充甘氨酸能在一定程度限制机体蛋氨酸水平。  图注：SAM与蛋氨酸互相转化的过程——SAM循环。Methionine: 蛋氨酸；homocysteine: 同型半胱氨酸 图源：https://www./figure/Two-of-indentified-SAM-cycle-related-enzyme-proteins-SAMS-and-MeSe-green-oval-shaped_fig7_236925221  甘氨酸延寿可也远不止限制蛋氨酸水平这一条，激活可促长生的自噬也是另一法门。 2018年发表于期刊Cell Reports的论文通过体外培养细胞及在体分析老年大鼠肝脏的代谢状态，发现甘氨酸经GNMT催化，反应生成的肌氨酸可以激活巨自噬[7]。  图注：GNMT酶催化甘氨酸反应，生成肌氨酸，激活自噬。Macroautophagy: 巨自噬；Lysosome: 溶酶体；Proteostasis: 蛋白质稳态 另外，2020年发表于Aging Cell的论文表明，抗衰物质亚精胺的延寿和上调自噬作用与GNMT的表达密切相关：在敲除GNMT的果蝇中，亚精胺竟无法起到其应有的抗衰效果[8]，这说明GNMT极有可能是亚精胺激活自噬的中间环节。  讲完甘氨酸的延寿原理，下面来看直观的延寿数据： 上下滑动，查看内容  除了其优秀的延寿效果，甘氨酸的突出之处还表现在其能改善多种衰老相关疾病。以下为几个例子： 上下滑动，查看内容  可以见得，甘氨酸能够在一定程度上改善代谢衰老、炎症与免疫衰老、细胞衰老、器官衰老及表型衰老这五大维度的衰老。 如果您想要服用或正在服用甘氨酸，但不确定其是否起效，欢迎关注时光派2023最新推出的“时光尺3.0”衰老评估体系。时光尺3.0以上述五维衰老评估为纲，纳入近170项检测指标，助您更加科学、系统地认知衰老，踏出呵护身体健康的第一步。 读到这里，或许您已对甘氨酸跃跃欲试，又或者产生了更多的疑问。 撰写这篇文章之前，小编在时光派会员群中收集了一些相关问题，在此给予解答，仅供参考。（大家的问题派派都有看到哦！由于问题有重复，所以这里仅选取部分问题解答。） Q 吃的量到底如何把握？还有服用方式细节，时间，是否随餐等等。 A 服用剂量根据服用需求决定。 根据2023年临床试验结果，100mg/kg/天甘氨酸和100mg/kg/天N-乙酰半胱氨酸（NAC）联用（称为GlyNAC）16周可改善24名老人的一系列衰老标志物[24]。此临床试验采用胶囊口服。按此摄入剂量，正常体重的人一天要吃十几克GlyNAC，未免有点夸张。 广泛查阅资料后，派派发现，在其它临床试验中，甘氨酸的剂量范围从1000mg/天到15000mg/天不等。 其中，连续三天每天服用3000mg甘氨酸可减少睡眠受限受试者的疲劳[25]；每天6000mg，持续八周可改善膀胱过度活动症患者的尿液储存系统[26]；而在一项涉及60名代谢综合征患者的独立临床研究中，患者收缩压因每天服用15000mg甘氨酸三个月而降低[27]。 除了论文之外，感谢万能的互联网，美国马萨诸塞州的一名慢性病管理医生Dr. Jin W. Sung在Youtube视频网站分享了他推荐的甘氨酸服用剂量：1800-2000mg/天，饭前30分钟或饭后2小时（也就是空腹）服用。供大家参考！ Q 甘氨酸比较安全，但 NAC 被 FDA 认为是药物。长期服用有问题吗？ A NAC不良反应与服用剂量有关。在1200 mg每天两次或更低的剂量下，NAC的耐受性良好，副作用并不常见，但可能包括恶心、呕吐、腹泻、短暂性皮疹、潮红、上腹痛和便秘。剂量更大时，N-乙酰半胱氨酸的耐受性通常很差，会产生头痛、耳鸣、荨麻疹、皮疹、寒战、发烧和类过敏反应（假性过敏反应）等副作用。NAC与硝酸甘油相互作用可能导致低血压[28]。要谨慎使用，注意剂量！ Q 吃胶原蛋白+肌酸能否替代吃甘氨酸？ A 派派的读者中就有类似这样吃的哦！ 甘氨酸的确是胶原蛋白的组成部分。若您已经在服用胶原蛋白、肌酸这类以甘氨酸为组成部分的补剂，建议控制剂量，安全谨慎为主哦！ 时光派点评 除甘氨酸+NAC的经典联用方案外，派派的读者中还有将此组合与AKG联用的朋友。三“药”联用，抗炎、抗氧化、激活线粒体[2]等作用似乎更强了。 总之，甘氨酸降低体内蛋氨酸水平及促进自噬，有效抗衰延寿。甜甜的它竟有此奇效，屏幕前的你心动了吗？ —— TIMEPIE —— 参考文献 [1] Plimmer, R.H.A. (1912). Plimmer, R.H.A.; Hopkins, F.G. (eds.). The chemical composition of the proteins. Monographs on biochemistry. Vol. Part I. Analysis (2nd ed.). London: Longmans, Green and Co. p. 82. [2] Kumar, P., Liu, C., Hsu, J. W., Chacko, S., Minard, C., Jahoor, F., & Sekhar, R. V. (2021). Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial. Clinical and translational medicine, 11(3), e372. doi: 10.1002/ctm2.372 [3] Johnson, A., & Cuellar, T. (2023). Glycine and aging: Evidence and mechanisms. Ageing Research Reviews, 87, 101922. doi: 10.1016/j.arr.2023.101922 [4] Parkhitko, A. A., Wang, L., Filine, E., Jouandin, P., Leshchiner, D., Binari, R., Asara, J. M., Rabinowitz, J. D., & Perrimon, N. (2021). A genetic model of methionine restriction extends Drosophila health- and lifespan. Proceedings of the National Academy of Sciences of the United States of America, 118(40), e2110387118. doi: 10.1073/pnas.2110387118 [5] Lee, B. C., Kaya, A., Ma, S., Kim, G., Gerashchenko, M. V., Yim, S. H., Hu, Z., Harshman, L. G., & Gladyshev, V. N. (2014). Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino-acid status. Nature communications, 5, 3592. doi: 10.1038/ncomms4592 [6] Miller, R. A., Buehner, G., Chang, Y., Harper, J. M., Sigler, R., & Smith-Wheelock, M. (2005). Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging cell, 4(3), 119–125. doi: 10.1111/j.1474-9726.2005.00152.x [7] Walters, R. O., Arias, E., Diaz, A., Burgos, E. S., Guan, F., Tiano, S., Mao, K., Green, C. L., Qiu, Y., Shah, H., Wang, D., Hudgins, A. D., Tabrizian, T., Tosti, V., Shechter, D., Fontana, L., Kurland, I. J., Barzilai, N., Cuervo, A. M., Promislow, D. E. L., … Huffman, D. M. (2018). Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans. Cell reports, 25(3), 663–676.e6. doi: 10.1016/j.celrep.2018.09.065 [8] Tain, L. S., Jain, C., Nespital, T., Froehlich, J., Hinze, Y., Grönke, S., & Partridge, L. (2020). Longevity in response to lowered insulin signaling requires glycine N-methyltransferase-dependent spermidine production. Aging cell, 19(1), e13043. doi: 10.1111/acel.13043 [9] Brind, J., Malloy, V., Augie, I., Caliendo, N., Vogelman, J. H., Zimmerman, J. A., & Orentreich, N. (2011). Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. [10] Edwards, C., Canfield, J., Copes, N., Brito, A., Rehan, M., & Lipps, D. et al. (2015). Mechanisms of amino acid-mediated lifespan extension in Caenorhabditis elegans. BMC Genetics, 16(1). doi: 10.1186/s12863-015-0167-2 [11] Obata, F., & Miura, M. (2015). Enhancing S-adenosyl-methionine catabolism extends Drosophila lifespan. Nature Communications, 6(1). doi: 10.1038/ncomms9332 [12] Liu, Y., Janssens, G., McIntyre, R., Molenaars, M., Kamble, R., & Gao, A. et al. (2019). Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion. PLOS Genetics, 15(3), e1007633. doi: 10.1371/journal.pgen.1007633 [13] Miller, R. A., Harrison, D. E., Astle, C. M., Bogue, M. A., Brind, J., Fernandez, E., Flurkey, K., Javors, M., Ladiges, W., Leeuwenburgh, C., Macchiarini, F., Nelson, J., Ryazanov, A. G., Snyder, J., Stearns, T. M., Vaughan, D. E., & Strong, R. (2019). Glycine supplementation extends lifespan of male and female mice. Aging cell, 18(3), e12953. doi: 10.1111/acel.12953 [14] Tain, L. S., Jain, C., Nespital, T., Froehlich, J., Hinze, Y., Grönke, S., & Partridge, L. (2020). Longevity in response to lowered insulin signaling requires glycine N-methyltransferase-dependent spermidine production. Aging cell, 19(1), e13043. doi: 10.1111/acel.13043 [15] Kumar, P., Osahon, O., & Sekhar, R. (2022). GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Mice Increases Length of Life by Correcting Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Abnormalities in Mitophagy and Nutrient Sensing, and Genomic Damage. Nutrients, 14(5), 1114. doi: 10.3390/nu14051114 [16] Rose, M., Madren, J., Bunzendahl, H., & Thurman, R. (1999). Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis, 20(5), 793-798. doi: 10.1093/carcin/20.5.793 [17] Ham, D., Murphy, K., Chee, A., Lynch, G., & Koopman, R. (2014). Glycine administration attenuates skeletal muscle wasting in a mouse model of cancer cachexia. Clinical Nutrition, 33(3), 448-458. doi: 10.1016/j.clnu.2013.06.013 [18] Gómez-Zamudio, J. H., García-Macedo, R., Lázaro-Suárez, M., Ibarra-Barajas, M., Kumate, J., & Cruz, M. (2015). Vascular endothelial function is improved by oral glycine treatment in aged rats. Canadian Journal of Physiology and Pharmacology, 93(6), 465-473. doi: 10.1139/cjpp-2014-0393 [19] Caldow, M., Ham, D., Godeassi, D., Chee, A., Lynch, G., & Koopman, R. (2016). Glycine supplementation during calorie restriction accelerates fat loss and protects against further muscle loss in obese mice. Clinical Nutrition, 35(5), 1118-1126. doi: 10.1016/j.clnu.2015.08.013 [20] Kim, M., Kim, H., & Jeong, H. (2015). Estrogen-like osteoprotective effects of glycine in in vitro and in vivo models of menopause. Amino Acids, 48(3), 791-800. doi: 10.1007/s00726-015-2127-6 [21] Lu, Y., Zhu, X., Li, J., Fang, R., Wang, Z., & Zhang, J. et al. (2017). Glycine prevents pressure overload induced cardiac hypertrophy mediated by glycine receptor. Biochemical Pharmacology, 123, 40-51. doi: 10.1016/j.bcp.2016.11.008 [22] Ullah, R., Jo, M., Riaz, M., Alam, S., Saeed, K., & Ali, W. et al. (2020). Glycine, the smallest amino acid, confers neuroprotection against d-galactose-induced neurodegeneration and memory impairment by regulating c-Jun N-terminal kinase in the mouse brain. Journal Of Neuroinflammation, 17(1). doi: 10.1186/s12974-020-01989-w [23] Chen, J., Yang, Y., Yang, Y., Dai, Z., Kim, I., Wu, G., & Wu, Z. (2021). Dietary Supplementation with Glycine Enhances Intestinal Mucosal Integrity and Ameliorates Inflammation in C57BL/6J Mice with High-Fat Diet–Induced Obesity. The Journal Of Nutrition, 151(7), 1769-1778. doi: 10.1093/jn/nxab058 [24] Kumar, P., Liu, C., Suliburk, J., Hsu, J. W., Muthupillai, R., Jahoor, F., Minard, C. G., Taffet, G. E., & Sekhar, R. V. (2023). Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. The journals of gerontology. Series A, Biological sciences and medical sciences, 78(1), 75–89. doi: 10.1093/gerona/glac135 [25] Bannai, M., Kawai, N., Ono, K., Nakahara, K., & Murakami, N. (2012). The Effects of Glycine on Subjective Daytime Performance in Partially Sleep-Restricted Healthy Volunteers. Frontiers In Neurology, 3. doi: 10.3389/fneur.2012.00061 [26] Sugaya, K., Oh-Oka, H., Yamada, T., Miyata, M., Ashitomi, K., Kadekawa, K., & Nishijima, S. (2021). Dietary glycine improves urine storage symptoms in urology outpatients. Journal Of Complementary And Integrative Medicine, 18(3), 617-620. doi: 10.1515/jcim-2020-0282 [27] Díaz-Flores, M., Cruz, M., Duran-Reyes, G., Munguia-Miranda, C., Loza-Rodríguez, H., Pulido-Casas, E., Torres-Ramírez, N., Gaja-Rodriguez, O., Kumate, J., Baiza-Gutman, L. A., & Hernández-Saavedra, D. (2013). Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure. Canadian journal of physiology and pharmacology, 91(10), 855–860. doi: 10.1139/cjpp-2012-0341 [28] Millea P. J. (2009). N-acetylcysteine: multiple clinical applications. American family physician, 80(3), 265–269. |
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