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導(dǎo)讀 前段日子，我們與大家一同盤點(diǎn)了抗氧化劑家族中的代表物質(zhì)，其中，一種天然來源于微藻的類胡蘿卜素[1]引起了筆者關(guān)注，它便是號稱“抗氧化王者”的蝦青素——活性氧清除能力是維生素C的6000倍，輔酶Q10的800倍，維生素E的550倍，多酚的200倍，花青素的150倍，α-硫辛酸的75倍[2]。  圖注：蝦青素分子結(jié)構(gòu)與從藻類提取制成的粉末 然而，今日蝦青素被“點(diǎn)到名”，可絕非因這一連串“晃到眩目”的漂亮數(shù)字（對于一項(xiàng)15年前發(fā)表在非核心期刊、使用初級檢測手法得到的結(jié)果，筆者持保留態(tài)度），而是在于其成為大名鼎鼎ITP計(jì)劃的“天選之子”。 作為國家官方機(jī)構(gòu)（美國國家老齡化研究所，NIA）主導(dǎo)的高規(guī)格大型衰老干預(yù)項(xiàng)目，ITP計(jì)劃在抗衰領(lǐng)域可謂舉足輕重，就驗(yàn)證物質(zhì)而言，經(jīng)層層篩選后，每期最終入選的不過也就三五種。在這樣激烈的角逐下，蝦青素能脫穎而出，躋身“ITP家族”，難免惹人多看兩眼。 雖說蝦青素最終驗(yàn)證結(jié)果遲遲未出，能不能成為下一個(gè)香餑餑還乾坤未定，但近期，ITP計(jì)劃“三大掌門人”之一、Paul F. Glenn衰老生物學(xué)研究中心主任Richard A. Miller在采訪中透露：“在我們未公布的干預(yù)試驗(yàn)結(jié)果里，部分物質(zhì)的結(jié)果令人興奮，其一是蝦青素?！?/span>  圖注：Richard A. Miller教授采訪截圖 那么，在NIA正式公布驗(yàn)證結(jié)果前，我們不妨先整理下近年來蝦青素在抗衰領(lǐng)域的重要發(fā)現(xiàn)，看看除了在老生常談的抗氧化上所向披靡，蝦青素還有哪些深藏不露的“御老之術(shù)”。 時(shí)光派的老讀者們對“炎性衰老”這一概念絕不會(huì)陌生。與衰老如影隨形并不斷積累的慢性炎癥，已被大量研究證實(shí)為心血管、神經(jīng)系統(tǒng)疾病以及癌癥、肌肉減少癥等多種疾病的誘發(fā)因素[3, 4]。 如何及時(shí)“摁住”炎癥肆虐的勢頭，對抗衰而言意義重大，而能夠降低機(jī)體炎癥水平（標(biāo)志物有CRP、TNF-α等）的抗炎物質(zhì)自是生逢其時(shí)。 在滿目琳瑯的抗炎物質(zhì)里，蝦青素依靠阻斷炎癥通路NF-κB與下游炎性因子基因表達(dá)（IL-6、TNF-α等）[5, 6]，以及對細(xì)胞內(nèi)COX-2（環(huán)氧合酶2）、NO（一氧化氮）的調(diào)控[7]，占據(jù)了抗炎戰(zhàn)區(qū)一席之地。 此外，多項(xiàng)人體臨床研究還表明，蝦青素可通過增強(qiáng)NK細(xì)胞、T細(xì)胞、B細(xì)胞等免疫細(xì)胞的數(shù)量或活性，調(diào)控免疫反應(yīng)[8]，幫助機(jī)體更好應(yīng)對炎癥這一不速之客。   2016年，諾貝爾生理學(xué)或醫(yī)學(xué)獎(jiǎng)再度被日本科學(xué)家摘得，“細(xì)胞自噬機(jī)制”也因此聲名大噪。 顧名思義，自噬=自我吞噬=吃掉自己，是細(xì)胞通過溶酶體降解廢棄蛋白質(zhì)、細(xì)胞器等大分子的“廢物再利用”過程[9]。在線蟲、果蠅、小鼠等一眾模式生物的研究中，都發(fā)現(xiàn)自噬對維持機(jī)體能量代謝穩(wěn)態(tài)、調(diào)控細(xì)胞命運(yùn)、延年益壽不可或缺[10, 11]，還是不少正當(dāng)紅抗衰物質(zhì)的靠山，如雷帕霉素、二甲雙胍、亞精胺、尿石素A。 興許是眼紅背靠自噬的兄弟們一路長虹，蝦青素把“打不過就加入”貫徹到底，轉(zhuǎn)身擁抱自噬。自2020年起，陸續(xù)有研究指出，蝦青素作為一種優(yōu)良的細(xì)胞自噬激活劑，可靶向線粒體，逆轉(zhuǎn)其因年齡增長導(dǎo)致的數(shù)量、質(zhì)量下降與功能障礙[12, 13]，并具有改善老年相關(guān)黃斑變性[14]、神經(jīng)退行性疾病[15, 16]的潛力。 其中，“蝦青素的神經(jīng)保護(hù)作用”尤得學(xué)界關(guān)注，畢竟對于不期而至的神經(jīng)退行性疾病，即便是頂級富豪比爾·蓋茨也曾在采訪中透露“這是他最害怕的事情”。如若蝦青素真能成為下一個(gè)“聰明藥”，必將極大造福全人類的健康未來。  圖注：頂級期刊Nature曾發(fā)行Insight特刊，對神經(jīng)退行性疾病給予高度關(guān)注  作為一種程序性死亡過程，細(xì)胞凋亡貫穿于我們生命的全周期。在發(fā)育早期，這一過程能幫助我們選擇性消除一些“不需要”的細(xì)胞，比如人類發(fā)育中手指間的皮膜（即蹼）；成年后，細(xì)胞凋亡又能幫助我們清除體內(nèi)已受損且無法被修復(fù)的細(xì)胞，并在預(yù)防癌癥中發(fā)揮重要作用[17, 18]。 對于這一調(diào)控動(dòng)物發(fā)育過程的必經(jīng)之路，蝦青素也當(dāng)仁不讓、參與其中。值得一提是，綜合當(dāng)下研究成果，蝦青素似乎能依據(jù)細(xì)胞狀態(tài)分別發(fā)出“促凋亡”或“抗凋亡”的指令。 例如，在癌細(xì)胞中，凋亡過程被阻止，細(xì)胞不受控制分裂進(jìn)而形成腫瘤，而蝦青素可通過上調(diào)BCL-2、Bax、Caspase-3等促凋亡蛋白的基因表達(dá)，誘導(dǎo)細(xì)胞發(fā)生凋亡[19-21]。而對于正常細(xì)胞，蝦青素則會(huì)“另眼相看”：調(diào)控p38/MAPK及PI3K/AKT信號通路，并下調(diào)促凋亡蛋白[22, 23]，避免過度凋亡誘導(dǎo)的神經(jīng)退行性疾病與多器官功能障礙綜合征[24]。  時(shí)光派點(diǎn)評 梳理完種種蝦青素的抗老法門，深感其深藏功與名，傳于街頭巷尾的出色抗氧化能力，不過只是其功效版圖中的光鮮一角。 但就如同Richard A. Miller教授在采訪中提及的那樣——“蝦青素是一種非處方物質(zhì)，非常普遍，無論從藥店或是保健品售賣平臺(tái)上，我們都可以輕松獲得?！蹦敲矗鎸@一品類繁多、流通已久的老牌物質(zhì)，想收獲ITP計(jì)劃中的意外延壽效果，是否又會(huì)是某種特殊來源、獨(dú)特結(jié)構(gòu)、特別工藝的蝦青素？ 不過吧，與其現(xiàn)在就糾結(jié)是哪種蝦青素，不如先等ITP計(jì)劃公布蝦青素的試驗(yàn)數(shù)據(jù)，是騾子還是馬，還得拉出來遛遛，真想看看蝦青素究竟憋了啥樣的大招。 —— TIMEPIE —— 參考文獻(xiàn) [1] Ambati, R. R., Phang, S. M., Ravi, S., & Aswathanarayana, R. G. (2014). Astaxanthin: sources, extraction, stability, biological activities and its commercial applications--a review. Marine drugs, 12(1), 128–152. https:///10.3390/md12010128 [2] Nishida, Y., Yamashita, E., & Miki, W. (2007). Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen using chemiluminescence detection system. Astaxanthin, 11, 16-20. https://doi:10.11501/10996240 [3] Ferrucci, L., & Fabbri, E. (2018). Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nature reviews. Cardiology, 15(9), 505–522. https:///10.1038/s41569-018-0064-2 [4] Chung, H. 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