Aging Well, Starting with the Heart: A Conversation with Dr. Joseph C. Wu, Director of the Stanford Cardiovascular Institute

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 Dr. Joseph C. Wu, 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.

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 changes like losing weight, cutting back on salt, and exercising more.

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.

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 “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.

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?

Joe 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. As countries grow wealthier, disparities in healthcare access often widen. 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.

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 enough because 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, gene therapy, or cell therapy.