此刻,筆者仍在案前碼字,掐指一算,歸鄉(xiāng)團聚已近在眼前,閉上眼仿佛美味佳肴正在招手,然而每日深受衰老科學文獻熏陶的筆者,自然是要時常提醒自己“管住嘴”:科學飲食限制 = 延年益壽。
能干預衰老、改變衰老進程的飲食方式不在少數(shù),從可謂“宇宙級最強”的熱量限制,到如地中海、DASH飲食等多種策略,我們多少都與大家聊過。除了上述這些抗衰業(yè)內公認度較高的飲食模式,也有一些飲食措施一直來飽受爭議,好比今天要和大家聊到的蛋白質與氨基酸限制飲食。
對于蛋白質與氨基酸限制方案,多數(shù)爭議點在于大家對蛋白質的傳統(tǒng)印象——生命活動必需物質,吃多也不會有發(fā)胖煩惱,小孩吃了躥個子,老人吃了走路穩(wěn)。然而,對于大多普通年輕人和抗衰需求日益強烈的中年人而言,蛋白質的真相可能并非如此。
蛋白質限制二三事:
吃少點,活久點
早在2005年,著名衰老領域頂級科學家Linda Partridge教授就發(fā)現(xiàn),卡路里限制不能完全解釋飲食限制的抗衰效果,當不同組別線蟲攝入相等熱量時,營養(yǎng)組成的差異會造成相當懸殊的長壽效果[1]。
圖注:不同營養(yǎng)組成時果蠅的壽命分析
之后,飲食抗衰研究愈加深入,更是凸顯了營養(yǎng)組分的重要性。2014年,澳大利亞營養(yǎng)學家Stephen Simpson教授證實,不同營養(yǎng)成分之間的比例才是生物健康長壽的決定性因素,并且應尤為關注蛋白質攝入量[2]。
在后續(xù)研究中,借助眾多模式生物,學者們陸續(xù)發(fā)現(xiàn)在不影響熱量攝入的前提下,僅需控制每日蛋白質攝入比例,就能延長如酵母、果蠅、小鼠的壽命[2-4]。
更甚者,蛋白質限制同樣被證明與人類衰老息息相關,遵循低蛋白攝入飲食的中年人群罹患心血管、癌癥等疾病風險更低,甚至死亡率也被大大降低[5-7]。例如一項對美國6000余名50歲及以上中老年人開展的長達18年的隨訪,發(fā)現(xiàn)高蛋白飲食使得中年人群(50-65歲)癌癥死亡率增加4倍,總體死亡率上升約75%[7]。
而對于該增益效果,推測由于限制蛋白質攝入量后,激活了GCN2(絲氨酸/蘇氨酸激酶)和轉錄因子ATF4,進而增加機體FGF21肝源性因子,并下調AKT-mTOR途徑[8, 9],還可能通過調節(jié)GHR(生長激素受體)—IGF-1信號轉導[10],延長了健康壽命。
特定氨基酸限制:
擒賊還需先擒王
既然蛋白質限制能給中年人帶去切實抗衰效果,那是否意味要眉毛胡子一把抓,限制攝入總量就可以?還不夠!在“高蛋白促衰”表象之下,我們更需找尋的是驅動這種反應的精確物質[11],做到“擒賊先擒王”。
下面為大家介紹的兩大類氨基酸,便是學界多年研究認為最可能的“賊王候選者”,合理控制其攝入,或許真能事半功倍。
No.1
蛋氨酸限制:多管齊下,不達長壽誓不罷休
作為人體必需氨基酸之一,蛋氨酸(又名為甲硫氨酸)多存在于豆類、魚類、奶制品中,并被發(fā)現(xiàn)限制其攝入量后能顯著延長多種模式生物壽命[12-14]。
例如,早在1993年,研究人員便嘗試利用大鼠去探索蛋氨酸限制的衰老干預效果,當大鼠飲食中蛋氨酸攝入量被從0.86%終生降低到0.17%后(下調約80%),雄性大鼠的壽命延長了近30%,并且“吃得少”也并未影響大鼠的正常生長[15]。
當然,限制蛋氨酸所得益處并非偶然,而是在于其對生物體內多種生物過程的調控。
· 蛋氨酸密碼子與蛋白質翻譯初始密碼子相同(均為AUG),限制蛋氨酸攝入后可顯著下調蛋白質合成,避免頻繁合成導致的錯誤堆積[16];
· 蛋氨酸可通過調節(jié)激素FGF21水平增加能量消耗[17];
· 蛋氨酸代謝物SAM(S-腺苷甲硫氨酸)和半胱氨酸可調控機體組蛋白和DNA甲基化,并影響體內氧化應激水平[8];
· 蛋氨酸限制還有效激活了大名鼎鼎的AMPK長壽通路[18]
甚至于,蛋氨酸還極可能是“王者”熱量限制抗衰背后的“終極答案”。2020年清北聯(lián)合刊發(fā)的一項重磅研究顯示,當研究人員給熱量限制中的酵母菌補充蛋氨酸后,熱量限制帶來的延壽效果不復存在[19]。
在與衰老短兵相見中,“蛋氨酸限制軍團”多管齊下,不達長壽誓不罷休。
No.2
BCAA(支鏈氨基酸)限制:為mTOR踩下生命剎車
BCAA并非是某種單一氨基酸,而是亮氨酸、異亮氨酸與纈氨酸的統(tǒng)稱,最早在20世紀60年代的一群肥胖人群血液中被過量檢出[20],且在后續(xù)研究中被發(fā)現(xiàn)與衰老相關的胰島素抵抗存在較大關聯(lián),被納入2型糖尿病的可能發(fā)病機制之一[2, 21]。先前筆者也曾就BCAA的體內代謝以及與常見養(yǎng)分感知系統(tǒng)關聯(lián)撰文詳述,可點擊回顧原文。
作為時光派的老讀者,當看到某一物質帶著“mTOR激活劑”標簽,幾乎下意識就會將其與“促衰”聯(lián)系起來,而BCAA作為一種強烈的mTORC1復合體激活劑,當過度攝入時,不僅是脂肪量增加、食欲亢進、胰島素抵抗這么簡單,更會帶來加速衰老的“惡劣副作用”[2, 22, 23]。
相反,BCAA限制的飲食策略被發(fā)現(xiàn)能提升早衰小鼠存活率、改善野生型小鼠機體代謝并延長其30%壽命[24],若向膳食中過多補充支鏈氨基酸,會誘導小鼠食欲過盛、壽命縮短[22]。
而上述這些“延年益壽”功效,正是因為控制BCAA的攝入量后,mTORC1被適度“剎車”[8],細胞與機體能在細水長流中延長健康期。想來儒家經典中庸之道,用在抗衰機制的解釋中,也頗為合適。
年終感恩炬制,終極實用篇!
我們如何開展蛋白質/氨基酸限制?
看到這里,也許有讀者坐不住了:“姜茶你寫了這么多,意思就讓我別吃蛋白質,別吃蛋氨酸,別吃BCAA了唄?!睂Υ?,筆者必須正名:“當然不是!”大到蛋白質作為三大營養(yǎng)素之一,是生物體的基本構成;小到蛋氨酸與BCAA都是人體必需氨基酸,身體也沒法合成,不吃就沒有。隨便挑出一樣,跟不上需求,身體馬上就要報警。
“限制不等于不吃,而是要正確吃,吃正確的東西,一以貫之去堅持”。這是筆者早先在會員群中與大家交流抗衰飲食心得時所說,也是個人貫徹于日常生活中的箴言。
那么,就蛋白質/氨基酸限制而言,我應該如何正確去吃:吃多少?吃什么?又或者,該如何評估自己是否適用于這一方案?
如果你有這樣的疑惑,那下面的這份資料剛好適合你!限于篇幅,姜茶將另附資料為大家一一道明??陕?lián)系好友列表中任意帶有“時光派”字樣的工作人員,發(fā)送暗號“蛋白質”,領取這份“《蛋白質/氨基酸限制食譜》”。PS:資料已優(yōu)先發(fā)送至時光派會員
如果還沒有小助理,可掃碼添加
歡迎大家來會員群或評論區(qū)與姜茶交流~~~
*2022衰老干預論壇的直播回放已上傳,點擊文末閱讀原文即可免費觀看。(專欄內更有重磅大咖課程等您解鎖~)
現(xiàn)時光派建立了論壇線上交流群。若您看完回放后想與老師們、抗衰同好更深入交流,歡迎聯(lián)系時光派工作人員入群(如無,請掃描上方二維碼添加)。
—— TIMEPIE ——
參考文獻
[1] Mair, W., Piper, M. D., & Partridge, L. (2005). Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS biology, 3(7), e223. https://doi.org/10.1371/journal.pbio.0030223
[2] Solon-Biet, S. M., McMahon, A. C., Ballard, J. W., Ruohonen, K., Wu, L. E., Cogger, V. C., Warren, A., Huang, X., Pichaud, N., Melvin, R. G., Gokarn, R., Khalil, M., Turner, N., Cooney, G. J., Sinclair, D. A., Raubenheimer, D., Le Couteur, D. G., & Simpson, S. J. (2014). The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell metabolism, 19(3), 418–430. https://doi.org/10.1016/j.cmet.2014.02.009
[3] Mirzaei, H., Raynes, R., & Longo, V. D. (2016). The conserved role of protein restriction in aging and disease. Current opinion in clinical nutrition and metabolic care, 19(1), 74–79. https://doi.org/10.1097/MCO.0000000000000239
[4] Kitada, M., Ogura, Y., Monno, I., & Koya, D. (2019). The impact of dietary protein intake on longevity and metabolic health. EBioMedicine, 43, 632–640. https://doi.org/10.1016/j.ebiom.2019.04.005
[5] Fung, T. T., van Dam, R. M., Hankinson, S. E., Stampfer, M., Willett, W. C., & Hu, F. B. (2010). Low-carbohydrate diets and all-cause and cause-specific mortality: two cohort studies. Annals of internal medicine, 153(5), 289–298. https://doi.org/10.7326/0003-4819-153-5-201009070-00003
[6] Lagiou, P., Sandin, S., Lof, M., Trichopoulos, D., Adami, H. O., & Weiderpass, E. (2012). Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study. BMJ (Clinical research ed.), 344, e4026. https://doi.org/10.1136/bmj.e4026
[7] Levine, M. E., Suarez, J. A., Brandhorst, S., Balasubramanian, P., Cheng, C. W., Madia, F., Fontana, L., Mirisola, M. G., Guevara-Aguirre, J., Wan, J., Passarino, G., Kennedy, B. K., Wei, M., Cohen, P., Crimmins, E. M., & Longo, V. D. (2014). Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell metabolism, 19(3), 407–417. https://doi.org/10.1016/j.cmet.2014.02.006
[8] Green, C. L., Lamming, D. W., & Fontana, L. (2022). Molecular mechanisms of dietary restriction promoting health and longevity. Nature reviews. Molecular cell biology, 23(1), 56–73. https://doi.org/10.1038/s41580-021-00411-4
[9] Mittendorfer, B., Klein, S., & Fontana, L. (2020). A word of caution against excessive protein intake. Nature reviews. Endocrinology, 16(1), 59–66. https://doi.org/10.1038/s41574-019-0274-7
[10] Mirzaei, H., Suarez, J. A., & Longo, V. D. (2014). Protein and amino acid restriction, aging and disease: from yeast to humans. Trends in endocrinology and metabolism: TEM, 25(11), 558–566. https://doi.org/10.1016/j.tem.2014.07.002
[11] Yap, Y.W., Rusu, P.M., Chan, A.Y. et al. (2020). Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution. Nature Communication 11, 2894. https://doi.org/10.1038/s41467-020-16568-z
[12] Parkhitko, A. A., Wang, L., Filine, E., Jouandin, P., Leshchiner, D., Binari, R., Perrimon, N. (2021). A genetic model of methionine restriction extends Drosophila health- and lifespan. Proceedings of the National Academy of Sciences, 118(40). http://www.pnas.org/content/118/40/e2110387118
[13] 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. https://doi.org/10.1038/ncomms4592
[14] 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. https://doi.org/10.1111/j.1474-9726.2005.00152.x
[15] Orentreich, N., Matias, J. R., DeFelice, A., & Zimmerman, J. A. (1993). Low methionine ingestion by rats extends life span. The Journal of nutrition, 123(2), 269–274. https://doi.org/10.1093/jn/123.2.269
[16] Mazor, K. M., Dong, L., Mao, Y., Swanda, R. V., Qian, S. B., & Stipanuk, M. H. (2018). Effects of single amino acid deficiency on mRNA translation are markedly different for methionine versus leucine. Scientific reports, 8(1), 8076. https://doi.org/10.1038/s41598-018-26254-2
[17] Douris, N., Stevanovic, D. M., Fisher, F. M., Cisu, T. I., Chee, M. J., Nguyen, N. L., Zarebidaki, E., Adams, A. C., Kharitonenkov, A., Flier, J. S., Bartness, T. J., & Maratos-Flier, E. (2015). Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice. Endocrinology, 156(7), 2470–2481. https://doi.org/10.1210/en.2014-2001
[18] Wang, S. Y., Wang, W. J., Liu, J. Q., Song, Y. H., Li, P., Sun, X. F., Cai, G. Y., & Chen, X. M. (2019). Methionine restriction delays senescence and suppresses the senescence-associated secretory phenotype in the kidney through endogenous hydrogen sulfide. Cell cycle (Georgetown, Tex.), 18(14), 1573–1587. https://doi.org/10.1080/15384101.2019.1618124
[19] Zou, K., Rouskin, S., Dervishi, K., McCormick, M. A., Sasikumar, A., Deng, C., Chen, Z., Kaeberlein, M., Brem, R. B., Polymenis, M., Kennedy, B. K., Weissman, J. S., Zheng, J., Ouyang, Q., & Li, H. (2020). Life span extension by glucose restriction is abrogated by methionine supplementation: Cross-talk between glucose and methionine and implication of methionine as a key regulator of life span. Science advances, 6(32), eaba1306. https://doi.org/10.1126/sciadv.aba1306
[20] Felig, P., Marliss, E., & Cahill, G. F., Jr (1969). Plasma amino acid levels and insulin secretion in obesity. The New England journal of medicine, 281(15), 811–816. https://doi.org/10.1056/NEJM196910092811503
[21] Ribeiro, R. V., Solon-Biet, S. M., Pulpitel, T., Senior, A. M., Cogger, V. C., Clark, X., O'Sullivan, J., Koay, Y. C., Hirani, V., Blyth, F. M., Seibel, M. J., Waite, L. M., Naganathan, V., Cumming, R. G., Handelsman, D. J., Simpson, S. J., & Le Couteur, D. G. (2019). Of Older Mice and Men: Branched-Chain Amino Acids and Body Composition. Nutrients, 11(8), 1882. https://doi.org/10.3390/nu11081882
[22] Solon-Biet, S. M., Cogger, V. C., Pulpitel, T., Wahl, D., Clark, X., Bagley, E., Gregoriou, G. C., Senior, A. M., Wang, Q. P., Brandon, A. E., Perks, R., O'Sullivan, J., Koay, Y. C., Bell-Anderson, K., Kebede, M., Yau, B., Atkinson, C., Svineng, G., Dodgson, T., Wali, J. A., … Simpson, S. J. (2019). Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control. Nature metabolism, 1(5), 532–545. https://doi.org/10.1038/s42255-019-0059-2
[23] Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., Haqq, A. M., Shah, S. H., Arlotto, M., Slentz, C. A., Rochon, J., Gallup, D., Ilkayeva, O., Wenner, B. R., Yancy, W. S., Jr, Eisenson, H., Musante, G., Surwit, R. S., Millington, D. S., Butler, M. D., … Svetkey, L. P. (2009). A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell metabolism, 9(4), 311–326. https://doi.org/10.1016/j.cmet.2009.02.002
[24] Richardson, N. E., Konon, E. N., Schuster, H. S., Mitchell, A. T., Boyle, C., Rodgers, A. C., Finke, M., Haider, L. R., Yu, D., Flores, V., Pak, H. H., Ahmad, S., Ahmed, S., Radcliff, A., Wu, J., Williams, E. M., Abdi, L., Sherman, D. S., Hacker, T., & Lamming, D. W. (2021). Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and lifespan in mice. Nature aging, 1(1), 73–86. https://doi.org/10.1038/s43587-020-00006-2