抗衰老从细胞做起？最全饮食干预细胞衰老盘点来袭！

编者按

自古代以来，不论寿命长短，每个人都有一个“长生不老”的梦想，而这份梦想投射到现代的科学社会，就变成了一个个抗衰研究。

而“细胞衰老学说”也是众多的抗衰学说中的一个，它在上个世纪刚提出的时候一度成为主流[1]，后来却又因为各种新机制的发现，渐渐被科研前进的洪流吞没。如今“沉舟侧畔千帆过”后，细胞衰老又一次走进大众的视野，成为最重要的衰老理论之一[2]。

而和“经历坎坷”的细胞衰老理论一样，抗衰的尽头还是生活，看过了那么多的药物才发现，生活才是最好的“干预”。

这篇饮食抗衰的综述，就为大家详细介绍了各种饮食成分和补剂对衰老细胞的作用。就让小编带着大家一起，看看怎么才能通过饮食延长寿命、健康衰老[3]。

早在1961年，就有科学家发现了细胞衰老的现象[4]，但是在当时，这只是一种相对表面的推测。经过60多年的沉淀和探索，细胞衰老的理念历经沉浮，终于浮出水面。

人衰老了以后就会产生各种各样的虚弱和病痛，并渐渐丧失工作的能力，而细胞的衰老也和人一样。

当细胞衰老了以后，就会积累各种损伤：端粒缩短和损伤、染色质结构改变、DNA 损伤和活性氧 (ROS) 积累、细胞周期抑制途径和β-半乳糖苷酶表达增加等，然后失去工作的能力：增殖分裂[5]。

图注：健康细胞在积累了大量“损伤”之后成为衰老细胞

虽然说细胞衰老是一个正常的生理过程，并且在伤口愈合、胚胎发育等过程中发挥着不可替代的作用[6-7]，但是瑜不掩瑕，衰老细胞的危害远比作用大：

衰老细胞不仅不能贡献新细胞出来，还会通过分泌SASP（促炎性因子等）来“感染”周围的细胞，诱导“二次衰老”[9]。在各种组织和器官中都发现，衰老细胞的积累与疾病以及整个机体死亡风险的增加相关[8]。

同时，老年个体因为免疫系统功能的降低，不足以清除所有衰老细胞，而衰老细胞的存在又会让免疫系统持续老化，细胞衰老和机体衰老互相促进，恶性循环[10]。

图注：衰老细胞对机体的影响

衰老细胞在我们看不到的地方默默“搞事情”，在整个生物体的衰老过程中推波助澜，那我们怎么才能悄悄“报复”回去呢？

其实“打击”衰老细胞很简单，健康的饮食就可以瞄准细胞衰老“开炮”，促进健康和长寿。

首先出场的是第一梯队，“元老级”营养素：碳水化合物、蛋白质和脂肪。

碳水化合物。虽然在大多数人的印象里，普通糖类在摄入过多时，会通过促进与年龄相关的糖尿病等加速衰老[11]。

但是！碳水化合物中其实还有不少不可忽视的“专精尖糖才”——多糖。从黄芪、不老莓、当归、枸杞等植物中提取出来的多糖可以通过调节mTOR/AMPK/SIRT1/NF-κB通路、抗氧化、减少SASP的表达等来打击衰老细胞[12-13]。

图注：多糖的广泛抗衰功效

蛋白质。和碳水“路人缘差”不一样的是，蛋白质一直广受“推崇”，尤其备受健身人士的喜爱，但是恰恰相反，高蛋白饮食反而会降低血浆中的NAD+水平，并促进炎性反应从而促进衰老[14]。

不过，就像碳水化合物一样，蛋白质也有自己的“秘密武器”——BCAA（亮氨酸、异亮氨酸、缬氨酸）。BCAA能一定程度上缓解ROS介导的氧化，以及起到保护端粒和改善线粒体生成等功能[15]（注：虽然本文中提到了BCAA的抗衰效果，但是也有不少研究探究了BCAA的促衰性[16]，屏幕前的大家还是要谨慎判断）。

图注：低蛋白饮食才更能减缓衰老

脂质。与碳水和蛋白需要“特殊成员加持”不一样的是，脂质，准确来说是其中的多不饱和脂肪酸，在维持生长和延缓衰老方面的关键作用早已得到了充分认可[17]，主要集中体现在抗炎和延长端粒两个方面。像omega-3脂肪酸和海洋n-3脂肪酸（鱼油）等，均能发挥强大的抗衰效果[18-19]。

图注：多不饱和脂肪酸的抗衰作用

看完了三大基础营养素，接下来向我们走来的则是一支“特种队伍”——膳食补剂，其中主要包括了维生素和矿物质等。和基础营养素队伍不同，补剂的队列（摄入量）非常精简，但是队伍里各个都是“人才”，能在抗击衰老细胞的“战斗”中提供“强化打击”。

首先是维生素小队。

●维生素D：能够上调由pAMPKα / SIRT1 / FOXO3a复合活性调节介导的IL-10和FOXO3a（长寿基因之一）表达，并增加端粒长度[20]；

●维生素E：具有强大的抗氧化活性，缓解细胞衰老[21]；

●维生素B2：能促进线粒体能量稳态，维持细胞功能[22]；

其次是矿物质小队。

●镁：能增强线粒体功能并防止氧化应激[23]；

●锌：能调节免疫系统，减少炎性衰老[24]；

再接下来是多酚小队。

多酚是一种常见于浆果、绿茶的物质，像蓝莓啊葡萄啊茶叶啊都富含多酚[25]。多酚主要通过调节几种细胞信号通路（如NRF2，NF-κB，mTOR，Sirtuins）以及自噬、免疫调节、细胞增殖和细胞凋亡等关键途径来减缓细胞衰老[26]。

同时，多酚中还有很大一部分具有“点对点”功效：衰老细胞清除剂Senolytics[27]。从槲皮素到茶多酚EGCG再到最近大火的葡萄籽成分PCC1，都能“战斗”在清除衰老细胞的第一线。

当然队伍里还有一些其他补剂，如益生菌等，能改善肠道生态失调，通过抑制肠道炎症来缓解细胞衰老和SASP的分泌[28]。

时光派点评

“日啖荔枝三百颗，不辞长作岭南人”，古人想借由饮食健康长寿，时至今日，人们也仍然在探究简单的饮食干预对衰老的影响。

读完本文，我们知道了什么是细胞衰老，以及日常饮食是怎样影响它的。但是我们究竟怎么吃才能更健康、更长寿？这还得看今年《Cell》的另一篇饮食综述《Nutrition, longevity and disease: From molecular mechanisms to interventions》[29]，文中提出了一款最新的科学食谱，能让每个照着吃的人最高延寿13年（详见文末“猜你想看”）。

通过这篇饮食抗衰综述我们也可以大胆展望，说不定在不久的将来，人们都可以将“抗衰”融入到生活，通过简简单单的饮食、运动、作息等，就能收获健康和长寿。

—— TIMEPIE ——

参考文献

[1] Cristofalo, V. J., Lorenzini, A., Allen, R. G., Torres, C., & Tresini, M. (2004). Replicative senescence: a critical review. Mechanisms of ageing and development, 125(10-11), 827–848. https://doi.org/10.1016/j.mad.2004.07.010

[2] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194–1217. https://doi.org/10.1016/j.cell.2013.05.039

[3] Diwan, B., & Sharma, R. (2022). Nutritional components as mitigators of cellular senescence in organismal aging: a comprehensive review. Food science and biotechnology, 31(9), 1089–1109. https://doi.org/10.1007/s10068-022-01114-y

[4] HAYFLICK, L., & MOORHEAD, P. S. (1961). The serial cultivation of human diploid cell strains. Experimental cell research, 25, 585–621. https://doi.org/10.1016/0014-4827(61)90192-6

[5] Campisi J. (2013). Aging, cellular senescence, and cancer. Annual review of physiology, 75, 685–705. https://doi.org/10.1146/annurev-physiol-030212-183653

[6] Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R. M., Vijg, J., Van Steeg, H., Dollé, M. E., Hoeijmakers, J. H., de Bruin, A., Hara, E., & Campisi, J. (2014). An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Developmental cell, 31(6), 722–733. https://doi.org/10.1016/j.devcel.2014.11.012

[7] Muñoz-Espín, D., Cañamero, M., Maraver, A., Gómez-López, G., Contreras, J., Murillo-Cuesta, S., Rodríguez-Baeza, A., Varela-Nieto, I., Ruberte, J., Collado, M., & Serrano, M. (2013). Programmed cell senescence during mammalian embryonic development. Cell, 155(5), 1104–1118. https://doi.org/10.1016/j.cell.2013.10.019

[8] Yousefzadeh, M. J., Zhao, J., Bukata, C., Wade, E. A., McGowan, S. J., Angelini, L. A., Bank, M. P., Gurkar, A. U., McGuckian, C. A., Calubag, M. F., Kato, J. I., Burd, C. E., Robbins, P. D., & Niedernhofer, L. J. (2020). Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice. Aging cell, 19(3), e13094. https://doi.org/10.1111/acel.13094

[9] Furman, D., Chang, J., Lartigue, L., Bolen, C. R., Haddad, F., Gaudilliere, B., Ganio, E. A., Fragiadakis, G. K., Spitzer, M. H., Douchet, I., Daburon, S., Moreau, J. F., Nolan, G. P., Blanco, P., Déchanet-Merville, J., Dekker, C. L., Jojic, V., Kuo, C. J., Davis, M. M., & Faustin, B. (2017). Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nature medicine, 23(2), 174–184. https://doi.org/10.1038/nm.4267

[10] Kale, A., Sharma, A., Stolzing, A., Desprez, P. Y., & Campisi, J. (2020). Role of immune cells in the removal of deleterious senescent cells. Immunity & ageing : I & A, 17, 16. https://doi.org/10.1186/s12979-020-00187-9

[11] Feinman, R. D., Pogozelski, W. K., Astrup, A., Bernstein, R. K., Fine, E. J., Westman, E. C., Accurso, A., Frassetto, L., Gower, B. A., McFarlane, S. I., Nielsen, J. V., Krarup, T., Saslow, L., Roth, K. S., Vernon, M. C., Volek, J. S., Wilshire, G. B., Dahlqvist, A., Sundberg, R., Childers, A., … Worm, N. (2015). Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition (Burbank, Los Angeles County, Calif.), 31(1), 1–13. https://doi.org/10.1016/j.nut.2014.06.011

[12] Miao, X. Y., Zhu, X. X., Gu, Z. Y., Fu, B., Cui, S. Y., Zu, Y., Rong, L. J., Hu, F., Chen, X. M., Gong, Y. P., & Li, C. L. (2022). Astragalus Polysaccharides Reduce High-glucose-induced Rat Aortic Endothelial Cell Senescence and Inflammasome Activation by Modulating the Mitochondrial Na+/Ca2+ Exchanger. Cell biochemistry and biophysics, 80(2), 341–353. https://doi.org/10.1007/s12013-021-01058-w

[13] Zhao, Y., Liu, X., Zheng, Y., Liu, W., & Ding, C. (2021). Aronia melanocarpa polysaccharide ameliorates inflammation and aging in mice by modulating the AMPK/SIRT1/NF-κB signaling pathway and gut microbiota. Scientific reports, 11(1), 20558. https://doi.org/10.1038/s41598-021-00071-6

[14] Seyedsadjadi, N., Berg, J., Bilgin, A. A., Braidy, N., Salonikas, C., & Grant, R. (2018). High protein intake is associated with low plasma NAD+ levels in a healthy human cohort. PloS one, 13(8), e0201968. https://doi.org/10.1371/journal.pone.0201968

[15] D'Antona, G., Ragni, M., Cardile, A., Tedesco, L., Dossena, M., Bruttini, F., Caliaro, F., Corsetti, G., Bottinelli, R., Carruba, M. O., Valerio, A., & Nisoli, E. (2010). Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell metabolism, 12(4), 362–372. https://doi.org/10.1016/j.cmet.2010.08.016

[16] Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019). From discoveries in ageing research to therapeutics for healthy ageing. Nature, 571(7764), 183–192. https://doi.org/10.1038/s41586-019-1365-2

[17] Lai, H. T., de Oliveira Otto, M. C., Lemaitre, R. N., McKnight, B., Song, X., King, I. B., Chaves, P. H., Odden, M. C., Newman, A. B., Siscovick, D. S., & Mozaffarian, D. (2018). Serial circulating omega 3 polyunsaturated fatty acids and healthy ageing among older adults in the Cardiovascular Health Study: prospective cohort study. BMJ (Clinical research ed.), 363, k4067. https://doi.org/10.1136/bmj.k4067

[18] Rodacki, C. L., Rodacki, A. L., Pereira, G., Naliwaiko, K., Coelho, I., Pequito, D., & Fernandes, L. C. (2012). Fish-oil supplementation enhances the effects of strength training in elderly women. The American journal of clinical nutrition, 95(2), 428–436. https://doi.org/10.3945/ajcn.111.021915

[19] Chen, J., Wei, Y., Chen, X., Jiao, J., & Zhang, Y. (2017). Polyunsaturated fatty acids ameliorate aging via redox-telomere-antioncogene axis. Oncotarget, 8(5), 7301–7314. https://doi.org/10.18632/oncotarget.14236

[20] Chen, L., Holder, R., Porter, C., & Shah, Z. (2021). Vitamin D3 attenuates doxorubicin-induced senescence of human aortic endothelial cells by upregulation of IL-10 via the pAMPKα/Sirt1/Foxo3a signaling pathway. PloS one, 16(6), e0252816. https://doi.org/10.1371/journal.pone.0252816

[21] Corina, A., Rangel-Zúñiga, O. A., Jiménez-Lucena, R., Alcalá-Díaz, J. F., Quintana-Navarro, G., Yubero-Serrano, E. M., López-Moreno, J., Delgado-Lista, J., Tinahones, F., Ordovás, J. M., López-Miranda, J., & Pérez-Martínez, P. (2019). Low Intake of Vitamin E Accelerates Cellular Aging in Patients With Established Cardiovascular Disease: The CORDIOPREV Study. The journals of gerontology. Series A, Biological sciences and medical sciences, 74(6), 770–777. https://doi.org/10.1093/gerona/gly195

[22] Nagano, T., Awai, Y., Kuwaba, S., Osumi, T., Mio, K., Iwasaki, T., & Kamada, S. (2021). Riboflavin transporter SLC52A1, a target of p53, suppresses cellular senescence by activating mitochondrial complex II. Molecular biology of the cell, 32(21), br10. https://doi.org/10.1091/mbc.E21-05-0262

[23] Villa-Bellosta R. (2020). Dietary magnesium supplementation improves lifespan in a mouse model of progeria. EMBO molecular medicine, 12(10), e12423. https://doi.org/10.15252/emmm.202012423

[24] Giacconi, R., Costarelli, L., Piacenza, F., Basso, A., Bürkle, A., Moreno-Villanueva, M., Grune, T., Weber, D., Stuetz, W., Gonos, E. S., Schön, C., Grubeck-Loebenstein, B., Sikora, E., Toussaint, O., Debacq-Chainiaux, F., Franceschi, C., Hervonen, A., Slagboom, E., Ciccarone, F., Zampieri, M., … Malavolta, M. (2018). Zinc-Induced Metallothionein in Centenarian Offspring From a Large European Population: The MARK-AGE Project. The journals of gerontology. Series A, Biological sciences and medical sciences, 73(6), 745–753. https://doi.org/10.1093/gerona/glx192

[25] Shimizu, C., Wakita, Y., Inoue, T., Hiramitsu, M., Okada, M., Mitani, Y., Segawa, S., Tsuchiya, Y., & Nabeshima, T. (2019). Effects of lifelong intake of lemon polyphenols on aging and intestinal microbiome in the senescence-accelerated mouse prone 1 (SAMP1). Scientific reports, 9(1), 3671. https://doi.org/10.1038/s41598-019-40253-x

[26] Cory, H., Passarelli, S., Szeto, J., Tamez, M., & Mattei, J. (2018). The Role of Polyphenols in Human Health and Food Systems: A Mini-Review. Frontiers in nutrition, 5, 87. https://doi.org/10.3389/fnut.2018.00087

[27] Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., O'Hara, S. P., LaRusso, N. F., Miller, J. D., Roos, C. M., Verzosa, G. C., LeBrasseur, N. K., Wren, J. D., Farr, J. N., Khosla, S., Stout, M. B., … Kirkland, J. L. (2015). The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging cell, 14(4), 644–658. https://doi.org/10.1111/acel.12344

[28] Kumar, R., Sharma, A., Gupta, M., Padwad, Y., & Sharma, R. (2020). Cell-Free Culture Supernatant of Probiotic Lactobacillus fermentum Protects Against H2O2-Induced Premature Senescence by Suppressing ROS-Akt-mTOR Axis in Murine Preadipocytes. Probiotics and antimicrobial proteins, 12(2), 563–576. https://doi.org/10.1007/s12602-019-09576-z

[29] Longo, V. D., & Anderson, R. M. (2022). Nutrition, longevity and disease: From molecular mechanisms to interventions. Cell, 185(9), 1455–1470. https://doi.org/10.1016/j.cell.2022.04.002