Remetinostat

编者按：今年九月，世界卫生组织（WHO）发布报告称，全球高血压患者人数已达14亿，但其中仅五分之一患者的病情得到了有效控制。作为冠状动脉疾病的主要诱因，高血压是全球范围内导致死亡的首要原因之一，尤其在老年人群中这一问题更加突出。鉴于高血压对全球公共健康的深远影响，我们采访了斯坦福大学心血管研究所主任、医学与放射学Simon H. Stertzer冠名教授Joseph Wu博士。作为全球心血管与再生医学领域的顶尖医生科学家，他在访谈中分享了他对健康老龄化及其他前沿议题的独到见解。Joseph Wu博士在成人先天性心脏病和心血管影像学领域具有深厚临床积累，他长期致力于阐明心血管疾病的病理机制、推动精准医疗实践，并通过创新替代策略来加速药物研发进程。其学术成果丰硕，迄今已发表六百余篇学术论文，连续七年（2018-2024）入选科睿唯安（Clarivate）“全球高被引科学家”（highly cited researchers）榜单，并荣获多项国际学术荣誉。此外，他还是生物技术公司Greenstone Biosciences的联合创始人。您好，感谢您接受我们的访谈，共同探讨健康老龄化这一重要议题。作为一名心脏病学领域的专家，您如何定义健康老龄化？Joseph Wu博士：我认为健康老龄化包含多重维度，其中身体健康、心理健康和社交健康是三个主要维度。身体健康意味着坚持经常锻炼、保持健康体重、均衡饮食、保证充足睡眠、戒烟戒酒等等。心理健康同样至关重要，这需要建立良好的社交网络、有效应对压力，以及通过阅读书籍、玩解谜游戏、打桥牌等方式保持认知刺激。此外，社交健康也不容忽视，这意味着与家人、朋友保持亲密联系，积极参与社区活动（如健身或志愿服务）。至少在我看来，这三者共同构成了健康老龄化的完整内涵。从心脏健康的角度看，心脏病发作是美国当前的头号致死因素，其次是癌症。为维护心脏健康，我们一般建议遵循美国心脏协会提出的“生命八要素”，具体包括：首先，应积极管理血压，高血压是导致冠状动脉疾病和大脑疾病的主要危险因素；其次，需注意预防糖尿病，避免摄入含糖饮料和高糖食品；第三，应严格控制胆固醇，过高水平的胆固醇会引发冠状动脉斑块形成，甚至危及生命；第四，应管理体重，体重指数（BMI）越高，罹患冠状动脉疾病与心脏病的风险也越大。前四项之外，其余四要素与生活方式息息相关：第五，改善饮食结构；第六，积极参与体育锻炼；第七，若有吸烟习惯应彻底戒除——近年来我们也强调，吸电子烟或大麻同样需要戒断；第八，保证充足睡眠，睡眠有助于修复身体机能，对整体健康极为重要。这八方面共同构成了“生命八要素”的整体框架。图片来源：123RF今年世界卫生组织在其最新发布的高血压报告中指出，全球约有14亿高血压患者，但其中仅有约五分之一的患者病情得到有效控制。众所周知，控制血压至关重要，但为何实现这一目标如此困难？Joseph Wu博士：这个问题并没有简单的答案。其中一个关键难点在于患者认知：许多人甚至根本不知道自己已患有高血压，这也正是为什么如今在药店等公共场所常设有自助血压检测站，目的就是帮助提升公众意识。一旦确诊高血压，我们虽然拥有多种不同类别的有效药物，但患者教育和用药依从性却是决定治疗效果的核心，而这正是医患之间需要密切协作的关键所在。就在昨天的门诊中，我接诊了两位血压控制不佳的患者。我们详细讨论了他们的用药方案、剂量调整策略以及后续的监测方法。这其实是一个持续沟通的过程，并不仅仅关乎血压或糖尿病等某个具体问题，更体现了医患关系的核心：双方必须在共同认知的基础上，用彼此理解的语言沟通，这样患者才会真正坚持用药，从而实现病情的有效控制。与此同时，患者自身也需在行为上做出积极改变，包括减轻体重、减少盐分摄入以及增加运动量。图片来源：123RF您的实验室是如何针对健康老龄化开展研究的？Joseph Wu博士：我们实验室专注于研发针对衰老过程的药物。由于这类药物需长期服用，其安全性要求极高，这与许多具有显著副作用的抗癌药物截然不同。我们主要探索两个方向：一是抑制炎症，减轻炎症反应有望减缓衰老进程；二是干预肌少症（sarcopenia），随着年龄增长，肌肉流失会加剧，若能通过药物减缓这一过程，将显著改善 衰老结局，因为肌肉量下降容易导致跌倒、骨折、住院及相关并发症。今年六月，我们还在《科学》杂志发表了一项研究成果。该研究耗时四、五年，成功开发出了能够将诱导性多能干细胞分化为受到广泛血管支配的心脏类器官与肝脏类器官的培养体系。我们筛选了约34种不同的体外诱导条件，最终找到一种诱导血管网络构建的因子组合，这一组合在心脏和肝脏类器官中都能生效。这项技术的重要意义在于：多数药物需先经肝脏代谢才作用于心脏，而我们的平台可在体外培养容器中使药物先经肝脏类器官代谢，产生的代谢物再输送至心脏类器官。这种设置更符合人体生理，更接近人体药物代谢过程。目前我们正将此平台广泛应用于内部药物研发。我们同时正在开展一项临床试验，将人胚胎干细胞来源的心肌细胞移植至心力衰竭患者体内。目前该研究仍处于早期阶段，还有许多问题尚未完全厘清。总体而言，再生医学领域最大的障碍是移植细胞的存活问题。无论是诱导多能干细胞分化的心肌细胞、肌肉细胞还是脑细胞，在移植后大量死亡的现象普遍存在。这是整个领域亟待解决的关键挑战。图片来源：123RF假设相关再生医学技术已然成熟，我们应当选择在何时对患者进行干预最为理想？是应当等到老年阶段症状显现之后才采取治疗措施，还是更早着手，例如在三、四十岁的年龄段，在心脏问题尚未显露时便提前介入？Joseph Wu博士：通常情况下，我们会在患者出现病症时进行治疗。若未出现症状，我们仍会倡导坚持运动、健康饮食、充足睡眠、戒烟限酒，并严格控制血压、糖尿病、体重及胆固醇指标。这些是疾病的主要诱因，且行为干预实施成本相对较低。唯有当这些手段用尽后，我们才会开始考虑再生医学、组织工程等前沿技术。作为心脏病专家，我始终强调防优于治的理念。防治心脏疾病的一端是饮食与运动干预，而另一端是前沿疗法。为何处于"中间地带"的疗法进展甚微？Joseph Wu博士：中间地带实际上已被现有常规药物占据，例如针对高胆固醇的他汀类药物，治疗高血压的血管紧张素转化酶抑制剂、β受体阻滞剂、钙通道阻滞剂等。我们已拥有诸多有效药物。但正因这些药物存在，业界在心血管疾病新药的研发投入上变得更加审慎。这是一个难题：在肿瘤领域，FDA常提供快速审评通道，研究终点更明确，且疗法多为针对特定基因突变的靶向治疗，因此这类“低垂果实”更具吸 引力。心血管疾病则更为复杂，通常涉及多基因作用，且受生活方式的强烈影响。因此我始终强调一级预防与良好习惯的重要性。就"中间地带"而言，企业望而却步是因为证明疗效需要规模庞大、成本高昂的临床试验。这导致部分药企转向罕见心血管疾病领域，而大多数常见心血管病领域因临床试验规模与成本限制，新研发项目相对稀少。图片来源：123RF感谢您的真知灼见。如果十年后我们再度聚首，继续探讨健康老龄化这一议题，您认为到那时我们会聚焦哪些议题？是会出现新的议题，还是总体方向将保持不变？Joseph Wu博士：从平均寿命来看，美国目前大约是78到79岁；日本和韩国位居前列，达到了84岁左右，中间存在五年的差距。美国的数值受到中青年过早死亡的影响，主要诱因包括冠心病、肺病、卒中等。我们在健康教育和医疗可及性方面仍有提升空间，目前医疗资源分配仍不均衡。若能提高医疗的可负担性与公平性，同时减少糖尿病、高血压、高胆固醇血症的发病率，并普及戒烟限酒、坚持运动的健康理念，或许能将平均寿命从79岁提升至80或81岁。尽管有人宣称，未来10到20年人工智能将推动人类预期寿命达到110岁甚至120岁，但作为一名医生，我认为这难以实现。少数可获得优质医疗资源且严格遵医嘱的人群或许能活到110岁，但从整体国民层面来看我认为这样的目标并不现实。像日本、韩国这些国家，在政府的强力支持、全民健康意识的提升、以及教育普及的共同作用下或许能在平均寿命上取得更好的成绩，但要实现全民普遍寿命达110-120岁仍极其困难。图片来源：123RF谁应当出资支持更长寿、更健康的生活？这些资金选择又将如何塑造创新方向，以及我们提供公平医疗的能力？Joseph Wu博士：我认为社会与个人需共同承担责任。政府与医疗体系可以开展公众教育，但若民众置若罔闻，就不会有任何改观。反之，如果人们有延长寿命的强烈意愿，却缺乏支持体系，同样难以达成目标。双方必须协同行动。这正是日本、韩国、瑞士、法国、西班牙等国家民众平均寿命指标更优的关键。在我看来，这些国家的政府体系与公共卫生教育更为完善。请允许我重申“生命八要素”（往期回顾：）。这些原则看似简单，但多数人却未能践行：改善饮食结构；保持运动习惯，短途出行以步代车；彻底戒烟，同样远离电子烟与大麻，研究表明大麻会引发血管炎症；保证充足睡眠，睡眠能修复身体机能，然而许多人却睡眠不足。此外还需关注高BMI的危害，这正是GLP-1药物对心血管、脑部及关节疾病产生重大影响的原因，体重超标会引发一系列继发性健康问题。在心脏病学领域，基础预防依然至关重要：预防糖尿病、高血压及高胆固醇血症。若能做好预防工作，其效益远胜于长寿药物。Aging Well, Starting with the Heart: A Conversation with Dr. Joseph C. Wu, Professor & Director of the Stanford Cardiovascular InstituteEditor’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: 123RFIn 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: 123RFHow 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 onScience. 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: 123RFSuppose 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 “low-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: 123RFThank 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: 123RFWho 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.参考资料：[1] Joseph Wu Lab.Retrieved October 17, 2025, fro https://med.stanford.edu/wulab.html免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。