上海
編者按：今年九月，世界衛(wèi)生組織（WHO）發(fā)布報(bào)告稱(chēng)，全球高血壓患者人數(shù)已達(dá)14億，但其中僅五分之一患者的病情得到了有效控制。作為冠狀動(dòng)脈疾病的主要誘因，高血壓是全球范圍內(nèi)導(dǎo)致死亡的首要原因之一，尤其在老年人群中這一問(wèn)題更加突出。鑒于高血壓對(duì)全球公共健康的深遠(yuǎn)影響，我們采訪了斯坦福大學(xué)心血管研究所主任、醫(yī)學(xué)與放射學(xué)Simon H. Stertzer冠名教授Joseph Wu博士。作為全球心血管與再生醫(yī)學(xué)領(lǐng)域的頂尖醫(yī)生科學(xué)家，他在訪談中分享了他對(duì)健康老齡化及其他前沿議題的獨(dú)到見(jiàn)解。
Joseph Wu博士在成人先天性心臟病和心血管影像學(xué)領(lǐng)域具有深厚臨床積累，他長(zhǎng)期致力于闡明心血管疾病的病理機(jī)制、推動(dòng)精準(zhǔn)醫(yī)療實(shí)踐，并通過(guò)創(chuàng)新替代策略來(lái)加速藥物研發(fā)進(jìn)程。其學(xué)術(shù)成果豐碩，迄今已發(fā)表六百余篇學(xué)術(shù)論文，連續(xù)七年（2018-2024）入選科睿唯安（Clarivate）“全球高被引科學(xué)家”（highly cited researchers）榜單，并榮獲多項(xiàng)國(guó)際學(xué)術(shù)榮譽(yù)。此外，他還是生物技術(shù)公司Greenstone Biosciences的聯(lián)合創(chuàng)始人。
您好，感謝您接受我們的訪談，共同探討健康老齡化這一重要議題。作為一名心臟病學(xué)領(lǐng)域的專(zhuān)家，您如何定義健康老齡化？
Joseph Wu博士：我認(rèn)為健康老齡化包含多重維度，其中身體健康、心理健康和社交健康是三個(gè)主要維度。身體健康意味著堅(jiān)持經(jīng)常鍛煉、保持健康體重、均衡飲食、保證充足睡眠、戒煙戒酒等等。心理健康同樣至關(guān)重要，這需要建立良好的社交網(wǎng)絡(luò)、有效應(yīng)對(duì)壓力，以及通過(guò)閱讀書(shū)籍、玩解謎游戲、打橋牌等方式保持認(rèn)知刺激。此外，社交健康也不容忽視，這意味著與家人、朋友保持親密聯(lián)系，積極參與社區(qū)活動(dòng)（如健身或志愿服務(wù)）。至少在我看來(lái)，這三者共同構(gòu)成了健康老齡化的完整內(nèi)涵。
從心臟健康的角度看，心臟病發(fā)作是美國(guó)當(dāng)前的頭號(hào)致死因素，其次是癌癥。為維護(hù)心臟健康，我們一般建議遵循美國(guó)心臟協(xié)會(huì)提出的“生命八要素”，具體包括：首先，應(yīng)積極管理血壓，高血壓是導(dǎo)致冠狀動(dòng)脈疾病和大腦疾病的主要危險(xiǎn)因素；其次，需注意預(yù)防糖尿病，避免攝入含糖飲料和高糖食品；第三，應(yīng)嚴(yán)格控制膽固醇，過(guò)高水平的膽固醇會(huì)引發(fā)冠狀動(dòng)脈斑塊形成，甚至危及生命；第四，應(yīng)管理體重，體重指數(shù)（BMI）越高，罹患冠狀動(dòng)脈疾病與心臟病的風(fēng)險(xiǎn)也越大。
前四項(xiàng)之外，其余四要素與生活方式息息相關(guān)：第五，改善飲食結(jié)構(gòu)；第六，積極參與體育鍛煉；第七，若有吸煙習(xí)慣應(yīng)徹底戒除——近年來(lái)我們也強(qiáng)調(diào)，吸電子煙或大麻同樣需要戒斷；第八，保證充足睡眠，睡眠有助于修復(fù)身體機(jī)能，對(duì)整體健康極為重要。這八方面共同構(gòu)成了“生命八要素”的整體框架。
圖片來(lái)源：123RF
今年世界衛(wèi)生組織在其最新發(fā)布的高血壓報(bào)告中指出，全球約有14億高血壓患者，但其中僅有約五分之一的患者病情得到有效控制。眾所周知，控制血壓至關(guān)重要，但為何實(shí)現(xiàn)這一目標(biāo)如此困難？
Joseph Wu博士：這個(gè)問(wèn)題并沒(méi)有簡(jiǎn)單的答案。其中一個(gè)關(guān)鍵難點(diǎn)在于患者認(rèn)知：許多人甚至根本不知道自己已患有高血壓，這也正是為什么如今在藥店等公共場(chǎng)所常設(shè)有自助血壓檢測(cè)站，目的就是幫助提升公眾意識(shí)。一旦確診高血壓，我們雖然擁有多種不同類(lèi)別的有效藥物，但患者教育和用藥依從性卻是決定治療效果的核心，而這正是醫(yī)患之間需要密切協(xié)作的關(guān)鍵所在。
就在昨天的門(mén)診中，我接診了兩位血壓控制不佳的患者。我們?cè)敿?xì)討論了他們的用藥方案、劑量調(diào)整策略以及后續(xù)的監(jiān)測(cè)方法。這其實(shí)是一個(gè)持續(xù)溝通的過(guò)程，并不僅僅關(guān)乎血壓或糖尿病等某個(gè)具體問(wèn)題，更體現(xiàn)了醫(yī)患關(guān)系的核心：雙方必須在共同認(rèn)知的基礎(chǔ)上，用彼此理解的語(yǔ)言溝通，這樣患者才會(huì)真正堅(jiān)持用藥，從而實(shí)現(xiàn)病情的有效控制。與此同時(shí)，患者自身也需在行為上做出積極改變，包括減輕體重、減少鹽分?jǐn)z入以及增加運(yùn)動(dòng)量。
圖片來(lái)源：123RF
您的實(shí)驗(yàn)室是如何針對(duì)健康老齡化開(kāi)展研究的？
Joseph Wu博士：我們實(shí)驗(yàn)室專(zhuān)注于研發(fā)針對(duì)衰老過(guò)程的藥物。由于這類(lèi)藥物需長(zhǎng)期服用，其安全性要求極高，這與許多具有顯著副作用的抗癌藥物截然不同。我們主要探索兩個(gè)方向：一是抑制炎癥，減輕炎癥反應(yīng)有望減緩衰老進(jìn)程；二是干預(yù)肌少癥（sarcopenia），隨著年齡增長(zhǎng)，肌肉流失會(huì)加劇，若能通過(guò)藥物減緩這一過(guò)程，將顯著改善 衰老結(jié)局，因?yàn)榧∪饬肯陆等菀讓?dǎo)致跌倒、骨折、住院及相關(guān)并發(fā)癥。
今年六月，我們還在《科學(xué)》雜志發(fā)表了一項(xiàng)研究成果。該研究耗時(shí)四、五年，成功開(kāi)發(fā)出了能夠?qū)⒄T導(dǎo)性多能干細(xì)胞分化為受到廣泛血管支配的心臟類(lèi)器官與肝臟類(lèi)器官的培養(yǎng)體系。我們篩選了約34種不同的體外誘導(dǎo)條件，最終找到一種誘導(dǎo)血管網(wǎng)絡(luò)構(gòu)建的因子組合，這一組合在心臟和肝臟類(lèi)器官中都能生效。這項(xiàng)技術(shù)的重要意義在于：多數(shù)藥物需先經(jīng)肝臟代謝才作用于心臟，而我們的平臺(tái)可在體外培養(yǎng)容器中使藥物先經(jīng)肝臟類(lèi)器官代謝，產(chǎn)生的代謝物再輸送至心臟類(lèi)器官。這種設(shè)置更符合人體生理，更接近人體藥物代謝過(guò)程。目前我們正將此平臺(tái)廣泛應(yīng)用于內(nèi)部藥物研發(fā)。
我們同時(shí)正在開(kāi)展一項(xiàng)臨床試驗(yàn)，將人胚胎干細(xì)胞來(lái)源的心肌細(xì)胞移植至心力衰竭患者體內(nèi)。目前該研究仍處于早期階段，還有許多問(wèn)題尚未完全厘清?？傮w而言，再生醫(yī)學(xué)領(lǐng)域最大的障礙是移植細(xì)胞的存活問(wèn)題。無(wú)論是誘導(dǎo)多能干細(xì)胞分化的心肌細(xì)胞、肌肉細(xì)胞還是腦細(xì)胞，在移植后大量死亡的現(xiàn)象普遍存在。這是整個(gè)領(lǐng)域亟待解決的關(guān)鍵挑戰(zhàn)。
圖片來(lái)源：123RF
假設(shè)相關(guān)再生醫(yī)學(xué)技術(shù)已然成熟，我們應(yīng)當(dāng)選擇在何時(shí)對(duì)患者進(jìn)行干預(yù)最為理想？是應(yīng)當(dāng)?shù)鹊嚼夏觌A段癥狀顯現(xiàn)之后才采取治療措施，還是更早著手，例如在三、四十歲的年齡段，在心臟問(wèn)題尚未顯露時(shí)便提前介入？
Joseph Wu博士：通常情況下，我們會(huì)在患者出現(xiàn)病癥時(shí)進(jìn)行治療。若未出現(xiàn)癥狀，我們?nèi)詴?huì)倡導(dǎo)堅(jiān)持運(yùn)動(dòng)、健康飲食、充足睡眠、戒煙限酒，并嚴(yán)格控制血壓、糖尿病、體重及膽固醇指標(biāo)。這些是疾病的主要誘因，且行為干預(yù)實(shí)施成本相對(duì)較低。唯有當(dāng)這些手段用盡后，我們才會(huì)開(kāi)始考慮再生醫(yī)學(xué)、組織工程等前沿技術(shù)。作為心臟病專(zhuān)家，我始終強(qiáng)調(diào)防優(yōu)于治的理念。
防治心臟疾病的一端是飲食與運(yùn)動(dòng)干預(yù)，而另一端是前沿療法。為何處于"中間地帶"的療法進(jìn)展甚微？
Joseph Wu博士：中間地帶實(shí)際上已被現(xiàn)有常規(guī)藥物占據(jù)，例如針對(duì)高膽固醇的他汀類(lèi)藥物，治療高血壓的血管緊張素轉(zhuǎn)化酶抑制劑、β受體阻滯劑、鈣通道阻滯劑等。我們已擁有諸多有效藥物。但正因這些藥物存在，業(yè)界在心血管疾病新藥的研發(fā)投入上變得更加審慎。
這是一個(gè)難題：在腫瘤領(lǐng)域，F(xiàn)DA常提供快速審評(píng)通道，研究終點(diǎn)更明確，且療法多為針對(duì)特定基因突變的靶向治療，因此這類(lèi)“低垂果實(shí)”更具吸 引力。
心血管疾病則更為復(fù)雜，通常涉及多基因作用，且受生活方式的強(qiáng)烈影響。因此我始終強(qiáng)調(diào)一級(jí)預(yù)防與良好習(xí)慣的重要性。就"中間地帶"而言，企業(yè)望而卻步是因?yàn)樽C明療效需要規(guī)模龐大、成本高昂的臨床試驗(yàn)。這導(dǎo)致部分藥企轉(zhuǎn)向罕見(jiàn)心血管疾病領(lǐng)域，而大多數(shù)常見(jiàn)心血管病領(lǐng)域因臨床試驗(yàn)規(guī)模與成本限制，新研發(fā)項(xiàng)目相對(duì)稀少。
圖片來(lái)源：123RF
感謝您的真知灼見(jiàn)。如果十年后我們?cè)俣染凼?，繼續(xù)探討健康老齡化這一議題，您認(rèn)為到那時(shí)我們會(huì)聚焦哪些議題？是會(huì)出現(xiàn)新的議題，還是總體方向?qū)⒈３植蛔儯?/strong>
Joseph Wu博士：從平均壽命來(lái)看，美國(guó)目前大約是78到79歲；日本和韓國(guó)位居前列，達(dá)到了84歲左右，中間存在五年的差距。美國(guó)的數(shù)值受到中青年過(guò)早死亡的影響，主要誘因包括冠心病、肺病、卒中等。我們?cè)诮】到逃歪t(yī)療可及性方面仍有提升空間，目前醫(yī)療資源分配仍不均衡。若能提高醫(yī)療的可負(fù)擔(dān)性與公平性，同時(shí)減少糖尿病、高血壓、高膽固醇血癥的發(fā)病率，并普及戒煙限酒、堅(jiān)持運(yùn)動(dòng)的健康理念，或許能將平均壽命從79歲提升至80或81歲。
盡管有人宣稱(chēng)，未來(lái)10到20年人工智能將推動(dòng)人類(lèi)預(yù)期壽命達(dá)到110歲甚至120歲，但作為一名醫(yī)生，我認(rèn)為這難以實(shí)現(xiàn)。少數(shù)可獲得醫(yī)療資源且嚴(yán)格遵醫(yī)囑的人群或許能活到110歲，但從整體國(guó)民層面來(lái)看我認(rèn)為這樣的目標(biāo)并不現(xiàn)實(shí)。像日本、韓國(guó)這些國(guó)家，在政府的強(qiáng)力支持、全民健康意識(shí)的提升、以及教育普及的共同作用下或許能在平均壽命上取得更好的成績(jī)，但要實(shí)現(xiàn)全民普遍壽命達(dá)110-120歲仍極其困難。
圖片來(lái)源：123RF
誰(shuí)應(yīng)當(dāng)出資支持更長(zhǎng)壽、更健康的生活？這些資金選擇又將如何塑造創(chuàng)新方向，以及我們提供公平醫(yī)療的能力？
Joseph Wu博士：我認(rèn)為社會(huì)與個(gè)人需共同承擔(dān)責(zé)任。政府與醫(yī)療體系可以開(kāi)展公眾教育，但若民眾置若罔聞，就不會(huì)有任何改觀。反之，如果人們有延長(zhǎng)壽命的強(qiáng)烈意愿，卻缺乏支持體系，同樣難以達(dá)成目標(biāo)。雙方必須協(xié)同行動(dòng)。這正是日本、韓國(guó)、瑞士、法國(guó)、西班牙等國(guó)家民眾平均壽命指標(biāo)更優(yōu)的關(guān)鍵。在我看來(lái)，這些國(guó)家的政府體系與公共衛(wèi)生教育更為完善。
請(qǐng)?jiān)试S我重申“生命八要素”。這些原則看似簡(jiǎn)單，但多數(shù)人卻未能踐行：改善飲食結(jié)構(gòu)；保持運(yùn)動(dòng)習(xí)慣，短途出行以步代車(chē)；徹底戒煙，同樣遠(yuǎn)離電子煙與大麻，研究表明大麻會(huì)引發(fā)血管炎癥；保證充足睡眠，睡眠能修復(fù)身體機(jī)能，然而許多人卻睡眠不足。此外還需關(guān)注高BMI的危害，這正是GLP-1藥物對(duì)心血管、腦部及關(guān)節(jié)疾病產(chǎn)生重大影響的原因，體重超標(biāo)會(huì)引發(fā)一系列繼發(fā)性健康問(wèn)題。在心臟病學(xué)領(lǐng)域，基礎(chǔ)預(yù)防依然至關(guān)重要：預(yù)防糖尿病、高血壓及高膽固醇血癥。若能做好預(yù)防工作，其效益遠(yuǎn)勝于長(zhǎng)壽藥物。
Aging Well, Starting with the Heart: A Conversation with Dr. Joseph C. Wu, Professor & Director of the Stanford Cardiovascular Institute
Editor’s Note:This September, the World Health Organization reported that 1.4 billion people live with hypertension worldwide, yet only one in five have it under control. As a major driver of coronary artery disease, hypertension remains a leading cause of death, especially among older adults. Against this backdrop, we spoke with Joseph C. Wu, MD, PhD, Director of the Stanford Cardiovascular Institute and the Simon H. Stertzer, MD, Professor of Medicine and Radiology at Stanford. One of the world’s leading physician-scientists in cardiovascular and regenerative medicine, Dr. Wu shares his perspective on healthy aging and beyond.
Greetings Joe, thanks for joining us to continue our discussion on healthy aging. As a cardiologist, what does healthy aging mean to you?
Joseph Wu:Thank you very much for inviting me.I think healthy aging involves multiple aspects, probably the big ones are physical, mental, and social.Physical means to exercise regularly, have a healthy weight, eat a balanced diet, get enough sleep, avoid alcohol, avoid smoking, and so forth. For mental health, which is equally important, it’s having a great social network, being able to manage stress, and having cognitive stimulation, reading books, doing puzzles, playing bridge, and more. And then the last one we like to emphasize is social health, which means strong relationships with family members, friends, and relatives, staying active in the community like going to the gym or volunteering. I would say it’s a component of all three, for me at least.
From the heart’s standpoint, heart attack is the number one killer in the U.S., followed by cancer. To maintain a healthy heart, we typically recommend the American Heart Association’s “Life’s Essential 8”. That is:make sure you manage your blood pressure.Hypertension is a big driver for coronary artery disease and also for brain disease.Avoid diabetes:avoid sugary beverages and foods with high sugar content.Control your cholesterol:because high cholesterol can cause plaques in the coronary arteries and kill the patient.Manage your weight:the higher your BMI, the higher the risk of coronary artery and heart disease.
Those are the first four. The other four are lifestyle: (5)have a better diet; (6)be more physically active; (7)if you’re smoking, quit.And more recently, if you’re vaping or taking marijuana, quit; and (8)get plenty of sleep,because sleep rejuvenates the body and is quite important. These are what we call the Life’s Essential 8.
Source: 123RF
In its most recent hypertension report, the World Health Organization estimated that about 1.4 billion people live with hypertension, but only 1 in 5 have it under control. We all know we should, but why is it so hard?
Joseph Wu:There’s no easy answer. One issue is patient awareness:many people don’t even know they have high blood pressure,which is why you see blood-pressure kiosks in places like CVS to raise awareness. Once diagnosed, we have many effective medications across different classes,but education and adherence are critical.This is where physicians need to work closely with patients.
Just yesterday in clinic I had two patients with blood-pressure problems; we went over their regimens, how we’d titrate doses, and how we’d monitor. It’s a constant dialogue. And it’s not just blood pressure or diabetes, it's the overall patient–physician relationship.Both sides need to be at the same table, speaking the same language,so patients actually take the medications and see improved control. At the same time,patients need to make behavioral changeslike losing weight, cutting back on salt, and exercising more.
Source: 123RF
How is your lab targeting healthy aging?
Joseph Wu:In our lab, we’re interested in developing drugs for aging. But because they’d be given long term, they must be very safe, unlike many cancer drugs with significant side effects.We’re mainly exploring two areas. First, inflammation:if you reduce inflammation, you may reduce senescence and improve the aging process.Second, sarcopenia:as people age, muscle wasting increases. Drugs that slow sarcopenia could improve outcomes, because loss of muscle mass leads to falls, fractures, hospitalizations, and complications.
This June, we also published a paper on
Science. That paper took us four to five years to develop a protocol to differentiate iPS cells into cardiac and liver organoids simultaneously, and to vascularize them. We screened about 34 different cocktails and identified one that works for both tissues.This matters because many drugs are first metabolized in the liver before reaching the heart. So we can now add a drug into the chamber, it’s metabolized by the liver organoid, and the metabolites then reach the heart organoid,a setup that’s far more physiologic and closer to human drug metabolism. We’re using this platform extensively in our in-house drug discovery.
We also have an ongoing trial injecting human embryonic stem cell–derived cardiomyocytes into patients with heart failure. It’s still early, and there’s a lot we don’t yet understand or have fully worked out. In general, the biggest barrier in regenerative medicine is cell survival. Many transplanted cells die after delivery. That’s true across iPSC-derived heart, muscle, and brain cells. This is a field-wide challenge that we need to solve.
Source: 123RF
Suppose they’re ready, when is the right time to treat patients? Should we wait until symptoms appear in older adults, or intervene earlier, say in their 30s or 40s, to keep the heart healthy before symptoms show up?
Joseph Wu:Typically, we treat when patients have a problem. If they don’t, we still advocate exercise, a healthy diet, plenty of sleep, avoiding alcohol and smoking, and maintaining good control of blood pressure, diabetes, weight, and cholesterol. Those are the primary drivers of disease and they’re relatively inexpensive to implement. It’s only when we run out of options that we start thinking about regenerative medicine, tissue engineering, or other “fancy” techniques.As a cardiologist, I still emphasize focusing on prevention first.
It seems like at one end we have diet and exercise. At the other end there are advanced therapies. Why don’t we hear a lot of progress in the “middle”?
Joseph Wu:In the middle are the common medications we already have, statins for high cholesterol; ACE inhibitors, beta blockers, calcium-channel blockers for high blood pressure, and so on. We have many effective drugs. Ironically, because these exist, many companies shy away from developing new cardiovascular drugs. It’s a conundrum: in oncology, the FDA often provides expedited pathways, endpoints can be clearer, and therapies are frequently mutation-targeted, so the “l(fā)ow-hanging fruit” is more attractive.
Cardiovascular disease is more complex, often polygenic and strongly influenced by lifestyle.So I keep emphasizing primary prevention and good habits.For the “middle,” companies often avoid it because proving benefit requires large, expensive trials. That’s why some pursue the extremes for rare cardiovascular diseases, while most bread-and-butter cardiovascular conditions see fewer new programs due to trial scale and cost.
Source: 123RF
Thank you for the insight. If we regroup in 10 years, what will we be talking about when we discuss healthy aging? Will it be different, or largely the same?
Joseph Wu:If you look at average lifespan, the U.S. is about 78–79; the best are Japan and South Korea at around 84, about a five-year gap. Our numbers in the US are affected by premature deaths in younger people. Premature death is driven by coronary heart disease, lung disease, stroke, and so forth. We could do better on education and access to care, which is not very equitable.If we make healthcare more affordable and equitable, and decrease diabetes, hypertension, high cholesterol, and educate people to exercise, not drink, not smoke, we might move from 79 to 80 or 81.
Some claim AI will push life expectancy to 110 or 120 in the next 10–20 years. As a physician, I don’t think that’s possible. A select group with excellent access and adherence might reach 110, but as a nation, I don’t think we can. Countries like Japan and South Korea can do better with stronger government support, awareness, and education, but reaching 110–120 broadly would still be very difficult.
Source: 123RF
Who should pay for longer, healthier lives? And how do these funding choices shape the direction of innovation and our capacity to deliver equitable care?
Joseph Wu:I think it’s both the society and the individual.Government and the healthcare infrastructure can educate the public, but if people don’t listen, nothing happens. Conversely, if individuals are highly motivated to extend longevity but there’s no supportive system, that won’t work either. Both sides have to move together. That’s why countries like Japan, South Korea, Switzerland, France, and Spain tend to have better outcomes: in my view, their government infrastructure and public-health education are stronger.
Let me re-emphasize Life’s Essential 8. It’s simple, but most people don’t follow it: Eat better;Be physically active, walk instead of driving short distances;Don’t smoke,the same goes for vaping and marijuana as our research shows marijuana causes vascular inflammation;Sleep enoughbecause sleep rejuvenates the body, yet many don’t get it. Then consider the consequences of high BMI. This is why the newer GLP-1 medications have such a big impact on cardiovascular, brain, and joint disease, as excess weight drives downstream problems.In cardiology, the basics still matter: avoid diabetes, hypertension, and hypercholesterolemia. If you do prevention well, it trumps longevity drugs.
參考資料：
[1] Joseph Wu Lab. Retrieved October 17, 2025, fro https://med.stanford.edu/wulab.html
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