—— TIMEPIE —— 参考文献 [1] Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018). Spermidine in health and disease. Science (New York, N.Y.), 359(6374), eaan2788. https://doi.org/10.1126/science.aan2788 [2] Hofer, S., Simon, A., Bergmann, M., Eisenberg, T., Kroemer, G., & Madeo, F. (2022). Mechanisms of spermidine-induced autophagy and geroprotection. Nature Aging, 2(12), 1112-1129. doi: 10.1038/s43587-022-00322-9 [3] Baek, A., Hong, J., Song, K., Jang, A., Kim, D., Chin, S., & Park, S. (2020). Spermidine attenuates bleomycin-induced lung fibrosis by inducing autophagy and inhibiting endoplasmic reticulum stress (ERS)-induced cell death in mice. Experimental &Amp; Molecular Medicine, 52(12), 2034-2045. doi: 10.1038/s12276-020-00545-z [4] Che, H., Ma, C., Li, H., Yu, F., Wei, Y., Chen, H., Wu, J., & Ren, Y. (2022). Rebalance of the Polyamine Metabolism Suppresses Oxidative Stress and Delays Senescence in Nucleus Pulposus Cells. Oxidative medicine and cellular longevity, 2022, 8033353. https://doi.org/10.1155/2022/8033353 [5] Yuan, X., Tian, G., Pei, X., Hu, X., & Wu, J. (2021). Spermidine induces cytoprotective autophagy of female germline stem cells in vitro and ameliorates aging caused by oxidative stress through upregulated sequestosome-1/p62 expression. Cell &Amp; Bioscience, 11(1). doi: 10.1186/s13578-021-00614-4 [6] Wirth, A., Wolf, B., Huang, C., Glage, S., Hofer, S., & Bankstahl, M. et al. (2021). Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length. Geroscience, 43(2), 673-690. doi: 10.1007/s11357-020-00310-0 [7] Scherz-Shouval, R., & Elazar, Z. (2011). Regulation of autophagy by ROS: physiology and pathology. Trends In Biochemical Sciences, 36(1), 30-38. doi: 10.1016/j.tibs.2010.07.007 [8] Jing, Y., Yan, J., Wang, Q., Chen, H., Ma, X., Yin, J., & Gao, L. (2018). Spermidine ameliorates the neuronal aging by improving the mitochondrial function in vitro. Experimental Gerontology, 108, 77-86. doi: 10.1016/j.exger.2018.04.005 [9] Eisenberg, T., Abdellatif, M., Schroeder, S., Primessnig, U., Stekovic, S., & Pendl, T. et al. (2016). Cardioprotection and lifespan extension by the natural polyamine spermidine. Nature Medicine, 22(12), 1428-1438. doi: 10.1038/nm.4222 [10] Qi, Y., Qiu, Q., Gu, X., Tian, Y., & Zhang, Y. (2016). ATM mediates spermidine-induced mitophagy via PINK1 and Parkin regulation in human fibroblasts. Scientific Reports, 6(1). doi: 10.1038/srep24700 [11] Puleston, D., Buck, M., Klein Geltink, R., Kyle, R., Caputa, G., & O’Sullivan, D. et al. (2019). Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation. Cell Metabolism, 30(2), 352-363.e8. doi: 10.1016/j.cmet.2019.05.003 [12] García-Prat, L., Martínez-Vicente, M., Perdiguero, E., Ortet, L., Rodríguez-Ubreva, J., & Rebollo, E. et al. (2016). Autophagy maintains stemness by preventing senescence. Nature, 529(7584), 37-42. doi: 10.1038/nature16187 [13] Balnis, J., Drake, L. A., Singer, D. V., Vincent, C. E., Korponay, T. C., D'Armiento, J., Lee, C. G., Elias, J. A., Singer, H. A., & Jaitovich, A. (2022). Deaccelerated Myogenesis and Autophagy in Genetically Induced Pulmonary Emphysema. American journal of respiratory cell and molecular biology, 66(6), 623–637. https://doi.org/10.1165/rcmb.2021-0351OC [14] Ao, Y., Zhang, J., Liu, Z., Qian, M., Li, Y., Wu, Z., Sun, P., Wu, J., Bei, W., Wen, J., Wu, X., Li, F., Zhou, Z., Zhu, W. G., Liu, B., & Wang, Z. (2019). Lamin A buffers CK2 kinase activity to modulate aging in a progeria mouse model. Science advances, 5(3), eaav5078. https://doi.org/10.1126/sciadv.aav5078 [15] Janssens, G., & Houtkooper, R. (2020). Identification of longevity compounds with minimized probabilities of side effects. Biogerontology, 21(6), 709-719. doi: 10.1007/s10522-020-09887-7 [16] Wirth, M., Benson, G., Schwarz, C., Köbe, T., Grittner, U., & Schmitz, D. et al. (2018). The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial. Cortex, 109, 181-188. doi: 10.1016/j.cortex.2018.09.014 [17] Wirth, M., Schwarz, C., Benson, G., Horn, N., Buchert, R., & Lange, C. et al. (2019). Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)—study protocol for a randomized controlled trial. Alzheimer's Research &Amp; Therapy, 11(1). doi: 10.1186/s13195-019-0484-1 [18] Pekar, T., Bruckner, K., Pauschenwein-Frantsich, S., Gschaider, A., Oppliger, M., & Willesberger, J. et al. (2020). The positive effect of spermidine in older adults suffering from dementia. Wiener Klinische Wochenschrift, 133(9-10), 484-491. doi: 10.1007/s00508-020-01758-y [19] Soda, K., Uemura, T., Sanayama, H., Igarashi, K., & Fukui, T. (2021). Polyamine-Rich Diet Elevates Blood Spermine Levels and Inhibits Pro-Inflammatory Status: An Interventional Study. Medical sciences (Basel, Switzerland), 9(2), 22. https://doi.org/10.3390/medsci9020022 [20] Matsumoto, M., & Benno, Y. (2004). Consumption of Bifidobacterium lactis LKM512 yogurt reduces gut mutagenicity by increasing gut polyamine contents in healthy adult subjects. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis, 568(2), 147-153. doi: 10.1016/j.mrfmmm.2004.07.016 [21] Matsumoto, M., Kitada, Y., & Naito, Y. (2019). Endothelial Function is improved by Inducing Microbial Polyamine Production in the Gut: A Randomized Placebo-Controlled Trial. Nutrients, 11(5), 1188. doi: 10.3390/nu11051188 [22] Rinaldi, F., Marzani, B., Pinto, D., & Ramot, Y. (2017). A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study. Dermatology Practical &Amp; Conceptual, 7(4), 17-21. doi: 10.5826/dpc.0704a05 [23] Eisenberg, T., Abdellatif, M., Schroeder, S., Primessnig, U., Stekovic, S., & Pendl, T. et al. (2016). Cardioprotection and lifespan extension by the natural polyamine spermidine. Nature Medicine, 22(12), 1428-1438. doi: 10.1038/nm.4222 [24] Kiechl, S., Pechlaner, R., Willeit, P., Notdurfter, M., Paulweber, B., & Willeit, K. et al. (2018). Higher spermidine intake is linked to lower mortality: a prospective population-based study. The American Journal Of Clinical Nutrition, 108(2), 371-380. doi: 10.1093/ajcn/nqy102 [25] Schroeder, S., Hofer, S. J., Zimmermann, A., Pechlaner, R., Dammbrueck, C., Pendl, T., Marcello, G. M., Pogatschnigg, V., Bergmann, M., Müller, M., Gschiel, V., Ristic, S., Tadic, J., Iwata, K., Richter, G., Farzi, A., Üçal, M., Schäfer, U., Poglitsch, M., Royer, P., … Madeo, F. (2021). Dietary spermidine improves cognitive function. Cell reports, 35(2), 108985. https://doi.org/10.1016/j.celrep.2021.108985 [26] Binh, P., Soda, K., Maruyama, C., & Kawakami, M. (2010). Relationship between food polyamines and gross domestic product in association with longevity in Asian countries. Health, 02(12), 1390-1396. doi: 10.4236/health.2010.212206 [27] Spermidine and Spermine Are Enriched in Whole Blood of Nona/Centenarians | Rejuvenation Research. (2023). Retrieved 23 February 2023, from https://www.liebertpub.com/doi/10.1089/rej.2012.1349 [28] Pietrocola, F., Pol, J., Vacchelli, E., Rao, S., Enot, D., & Baracco, E. et al. (2016). Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. Cancer Cell, 30(1), 147-160. doi: 10.1016/j.ccell.2016.05.016 [29] Spermidine reduces cancer-related mortality in humans. (2023). Autophagy. Retrieved from https://www.tandfonline.com/doi/full/10.1080/15548627.2018.1539592 [30] Gobert, A., Latour, Y., Asim, M., Barry, D., Allaman, M., & Finley, J. et al. (2022). Protective Role of Spermidine in Colitis and Colon Carcinogenesis. Gastroenterology, 162(3), 813-827.e8. doi: 10.1053/j.gastro.2021.1
Top Comments Comment 完美人生＝健康+快乐+靓丽+青春 From 云南 Reply Like 2 直接吞精，是否比富含亚精胺的天然食物来得更直接效果更好？ 1条回复
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https://mp.weixin.qq.com/s/N7bSm6OSvaiAfcskTBMhzQ
顶级期刊Science发表文章，在回顾130余篇科研进展后，肯定了它对生物体的健康价值
亚精胺，300多年前从显微镜之父列文虎克的精液中被发现，流淌在每个甜蜜的夜晚，它的独特气味也将在未来2到3个月四处飘荡。
2016年，诺贝尔生理学与医学奖花落细胞自噬研究，这让能“激活细胞自噬”的亚精胺声名大噪。仅2年后，顶级期刊Science发表文章，在回顾130余篇科研进展后，肯定了亚精胺对生物体的健康价值[1]。
随即，亚精胺更是得到曾成功打捞抗衰分子AKG（注：α-酮戊二酸，一种线粒体中间产物）、新加坡著名学者Brian Kennedy教授青眼，跻身抗衰种子物质后备军。
同样看好亚精胺抗衰潜力的，还有深耕细胞自噬与调控20多年的Frank Madeo教授，在他看来“亚精胺是一种真正的老年保护剂”。
不久前，Madeo教授团队在Nature Aging发表综述，全面梳理了亚精胺在诱导自噬和老年保护上的作用，并就其在人体临床中的应用、是否促进肿瘤生长等热点话题进行分析[2]。同时在文献之外，派派也为大家整理了生活中常见富含亚精胺的食物，可至文末阅读。
近年来，亚精胺被发现在代谢、炎症、免疫稳态丧失等方面具有预防、甚至治疗功效。而对衰老，这一众多老年疾病的最大风险因素，亚精胺能多面调控衰老标识、延长生物体寿命。
No.1 直击九大衰老标识
包括细胞衰老、端粒磨损在内的九大标识，堪称衰老领域最经典的生物指标，有了它们，我们在干预衰老上才能有方向，而亚精胺对这些重要标识几乎都能起到不错的调控作用。
细胞衰老 细胞衰老促使细胞周期与分子特征发生改变，并产生特定的衰老相关分泌表型，加速机体整体性衰老。
可喜的是，在体外细胞与小鼠模型中，研究结果均发现亚精胺显著减少了衰老细胞数量[3, 4]。例如，在雌性生殖系干细胞中，亚精胺显著降低了细胞衰老标志物p16水平[5]。
端粒磨损 端粒位于染色体末端，在细胞复制过程中起到保护性作用，但由于成人体内几乎不再表达端粒酶，因此随着年龄增长，我们身体中的端粒会逐渐缩短。
然而，当衰老小鼠连续6个月补充亚精胺后，端粒缩短速度被明显延缓，达到年轻小鼠相似水平[6]。这可能与亚精胺促进自噬、调控机体活性氧水平有关[7]。
线粒体功能障碍 在衰老过程中，线粒体结构及功能障碍并不罕见，而线粒体异常又会通过降低细胞能量供应、长期激活促炎反应等，加速机体衰老。
于是，长期来学者们都在找寻方法去修复这一重要的细胞器，其间，亚精胺脱颖而出，有效改善了衰老细胞与模式生物（果蝇、小鼠）的线粒体功能[8-10]，恢复了线粒体蛋白的正常生物合成[11]。
干细胞耗竭 细胞分化潜能在生物老化过程中逐渐丧失，导致老年生物体无法及时修复组织损伤、改善体内炎症环境，但亚精胺却似乎有一种能“拨回”细胞分化潜能的力量。
通过诱导细胞自噬，亚精胺恢复了肌肉干细胞的再生功能、促进肌肉生成，是逆转肌少症的有力候选物质[12, 13]。
No.2 干预衰老，延长寿命少不了
当谈及某个潜在老年保护物质或干预措施，我们总会期待它能延长寿命（最大寿命/健康寿命），而亚精胺凭借激活自噬及调控机体信号通路中的转录因子、能量感知通路（AMPK和mTORC1）等，多方恢复生物机体代谢健康。
在茫茫物质海洋里好不容易打捞的抗衰成分，不少会在人体实验这临门一脚上功亏一篑，但亚精胺却成功受住了考验。
目前，在人体临床试验中，亚精胺被发现：
No.1 改善记忆力、认知功能
平均年龄超过70岁的老年人群，连续3个月或12个月摄入高亚精胺含量的小麦胚芽提取物后，老人们衰老相关的认知障碍得到改善，且期间未发生任何不良反应[15-18]。
连续一年通过摄入纳豆补充亚精胺，受试者机体免疫系统的淋巴细胞异常活化现象得到改善，显著降低身体慢性炎症[19]。
通过联用精氨酸和动物双歧杆菌乳酸亚种酸奶提升人体肠道内亚精胺含量，发现显著改善了受试者内皮功能与血脂状况[20, 21]。
在一项随机、安慰剂、双盲高级别人体临床中，亚精胺被证实能延长毛囊生长期，辅助脱发治疗[22]。
并且，健康的高龄或百岁老人身体的亚精胺含量，也相比同年龄段、非健康状态的对照人群要高出不少[27]。
不过，就是这样既能灵活大脑，又能健康心血管，还意外能防脱发的亚精胺，在人体中，含量却会因衰老渐渐变得不够，想保持健康，及时补上很必要。
至于摄取亚精胺的途径，文献之外，贴心的派派已为大家整理了些富含亚精胺的天然食物，不妨下一餐开始对照着吃起来（PS：表格信息仍不足，欢迎大家评论区补充）。要是怕吃不够，还可以选择市面上正规的补充剂适当服用，在这不做具体品牌推荐。
最后想说的是，参照Frank Madeo教授的建议——“不建议患有肿瘤、癌症或仍处于康复期的人群额外补充亚精胺”。
不过，若要盖棺定论，说亚精胺促进癌症发展，还为时尚早，相反，部分研究中，亚精胺还起到了抑制肿瘤发展的作用[28-30]。只能讲，对这个300多年前就被发现、生活中广泛存在的物质，我们还需要更多研究。
—— TIMEPIE ——
参考文献 [1] Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018). Spermidine in health and disease. Science (New York, N.Y.), 359(6374), eaan2788. https://doi.org/10.1126/science.aan2788 [2] Hofer, S., Simon, A., Bergmann, M., Eisenberg, T., Kroemer, G., & Madeo, F. (2022). Mechanisms of spermidine-induced autophagy and geroprotection. Nature Aging, 2(12), 1112-1129. doi: 10.1038/s43587-022-00322-9 [3] Baek, A., Hong, J., Song, K., Jang, A., Kim, D., Chin, S., & Park, S. (2020). Spermidine attenuates bleomycin-induced lung fibrosis by inducing autophagy and inhibiting endoplasmic reticulum stress (ERS)-induced cell death in mice. Experimental &Amp; Molecular Medicine, 52(12), 2034-2045. doi: 10.1038/s12276-020-00545-z [4] Che, H., Ma, C., Li, H., Yu, F., Wei, Y., Chen, H., Wu, J., & Ren, Y. (2022). Rebalance of the Polyamine Metabolism Suppresses Oxidative Stress and Delays Senescence in Nucleus Pulposus Cells. Oxidative medicine and cellular longevity, 2022, 8033353. https://doi.org/10.1155/2022/8033353 [5] Yuan, X., Tian, G., Pei, X., Hu, X., & Wu, J. (2021). Spermidine induces cytoprotective autophagy of female germline stem cells in vitro and ameliorates aging caused by oxidative stress through upregulated sequestosome-1/p62 expression. Cell &Amp; Bioscience, 11(1). doi: 10.1186/s13578-021-00614-4 [6] Wirth, A., Wolf, B., Huang, C., Glage, S., Hofer, S., & Bankstahl, M. et al. (2021). Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length. Geroscience, 43(2), 673-690. doi: 10.1007/s11357-020-00310-0 [7] Scherz-Shouval, R., & Elazar, Z. (2011). Regulation of autophagy by ROS: physiology and pathology. Trends In Biochemical Sciences, 36(1), 30-38. doi: 10.1016/j.tibs.2010.07.007 [8] Jing, Y., Yan, J., Wang, Q., Chen, H., Ma, X., Yin, J., & Gao, L. (2018). Spermidine ameliorates the neuronal aging by improving the mitochondrial function in vitro. Experimental Gerontology, 108, 77-86. doi: 10.1016/j.exger.2018.04.005 [9] Eisenberg, T., Abdellatif, M., Schroeder, S., Primessnig, U., Stekovic, S., & Pendl, T. et al. (2016). Cardioprotection and lifespan extension by the natural polyamine spermidine. Nature Medicine, 22(12), 1428-1438. doi: 10.1038/nm.4222 [10] Qi, Y., Qiu, Q., Gu, X., Tian, Y., & Zhang, Y. (2016). ATM mediates spermidine-induced mitophagy via PINK1 and Parkin regulation in human fibroblasts. Scientific Reports, 6(1). doi: 10.1038/srep24700 [11] Puleston, D., Buck, M., Klein Geltink, R., Kyle, R., Caputa, G., & O’Sullivan, D. et al. (2019). Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation. Cell Metabolism, 30(2), 352-363.e8. doi: 10.1016/j.cmet.2019.05.003 [12] García-Prat, L., Martínez-Vicente, M., Perdiguero, E., Ortet, L., Rodríguez-Ubreva, J., & Rebollo, E. et al. (2016). Autophagy maintains stemness by preventing senescence. Nature, 529(7584), 37-42. doi: 10.1038/nature16187 [13] Balnis, J., Drake, L. A., Singer, D. V., Vincent, C. E., Korponay, T. C., D'Armiento, J., Lee, C. G., Elias, J. A., Singer, H. A., & Jaitovich, A. (2022). Deaccelerated Myogenesis and Autophagy in Genetically Induced Pulmonary Emphysema. American journal of respiratory cell and molecular biology, 66(6), 623–637. https://doi.org/10.1165/rcmb.2021-0351OC [14] Ao, Y., Zhang, J., Liu, Z., Qian, M., Li, Y., Wu, Z., Sun, P., Wu, J., Bei, W., Wen, J., Wu, X., Li, F., Zhou, Z., Zhu, W. G., Liu, B., & Wang, Z. (2019). Lamin A buffers CK2 kinase activity to modulate aging in a progeria mouse model. Science advances, 5(3), eaav5078. https://doi.org/10.1126/sciadv.aav5078 [15] Janssens, G., & Houtkooper, R. (2020). Identification of longevity compounds with minimized probabilities of side effects. Biogerontology, 21(6), 709-719. doi: 10.1007/s10522-020-09887-7 [16] Wirth, M., Benson, G., Schwarz, C., Köbe, T., Grittner, U., & Schmitz, D. et al. (2018). The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial. Cortex, 109, 181-188. doi: 10.1016/j.cortex.2018.09.014 [17] Wirth, M., Schwarz, C., Benson, G., Horn, N., Buchert, R., & Lange, C. et al. (2019). Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)—study protocol for a randomized controlled trial. Alzheimer's Research &Amp; Therapy, 11(1). doi: 10.1186/s13195-019-0484-1 [18] Pekar, T., Bruckner, K., Pauschenwein-Frantsich, S., Gschaider, A., Oppliger, M., & Willesberger, J. et al. (2020). The positive effect of spermidine in older adults suffering from dementia. Wiener Klinische Wochenschrift, 133(9-10), 484-491. doi: 10.1007/s00508-020-01758-y [19] Soda, K., Uemura, T., Sanayama, H., Igarashi, K., & Fukui, T. (2021). Polyamine-Rich Diet Elevates Blood Spermine Levels and Inhibits Pro-Inflammatory Status: An Interventional Study. Medical sciences (Basel, Switzerland), 9(2), 22. https://doi.org/10.3390/medsci9020022 [20] Matsumoto, M., & Benno, Y. (2004). Consumption of Bifidobacterium lactis LKM512 yogurt reduces gut mutagenicity by increasing gut polyamine contents in healthy adult subjects. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis, 568(2), 147-153. doi: 10.1016/j.mrfmmm.2004.07.016 [21] Matsumoto, M., Kitada, Y., & Naito, Y. (2019). Endothelial Function is improved by Inducing Microbial Polyamine Production in the Gut: A Randomized Placebo-Controlled Trial. Nutrients, 11(5), 1188. doi: 10.3390/nu11051188 [22] Rinaldi, F., Marzani, B., Pinto, D., & Ramot, Y. (2017). A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study. Dermatology Practical &Amp; Conceptual, 7(4), 17-21. doi: 10.5826/dpc.0704a05 [23] Eisenberg, T., Abdellatif, M., Schroeder, S., Primessnig, U., Stekovic, S., & Pendl, T. et al. (2016). Cardioprotection and lifespan extension by the natural polyamine spermidine. Nature Medicine, 22(12), 1428-1438. doi: 10.1038/nm.4222 [24] Kiechl, S., Pechlaner, R., Willeit, P., Notdurfter, M., Paulweber, B., & Willeit, K. et al. (2018). Higher spermidine intake is linked to lower mortality: a prospective population-based study. The American Journal Of Clinical Nutrition, 108(2), 371-380. doi: 10.1093/ajcn/nqy102 [25] Schroeder, S., Hofer, S. J., Zimmermann, A., Pechlaner, R., Dammbrueck, C., Pendl, T., Marcello, G. 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