Intro. [Recording date: May 28, 2025.]
Russ Roberts: Today is May 28th, 2025, and I’m thrilled to welcome back Dr. Eric Topol, a notable physician and author. This marks his fourth time on the show, having last joined us in June 2019 to discuss his book, Deep Medicine.
Today, we’ll delve into his latest work, Superagers: An Evidence-Based Approach to Longevity. Eric, it’s great to have you back on EconTalk.
Eric Topol: Thanks, Russ! It’s fantastic to be here again.
Russ Roberts: Your new book is an exceptional compendium of our current understanding—and misunderstanding—of human health. Two points struck me after reading: the intricate complexity of biological processes that we barely grasped four or five decades ago, and the paradox that despite our vast knowledge growth, fundamental aspects remain elusive. Would you say that’s a fair assessment?
Eric Topol: Absolutely, I couldn’t agree more.
Russ Roberts: Please, elaborate on that.
Eric Topol: One major misconception is the timeline for the onset of chronic diseases like cancer, cardiovascular issues, and neurodegenerative disorders. As a cardiologist, we often attribute a heart attack to recent stressors, but the reality is these conditions can develop over decades—often over 20 years.
Another prevalent myth is the belief that our genes solely dictate our health. Contrary to this notion, findings from studies, such as the wellderly study involving nearly 1,400 individuals over the age of 85 who had never taken medication, revealed little genetic predisposition in their genome sequences. Many myths persist, particularly regarding our understanding of the immune system’s role in aging. We have yet to measure how it fluctuates as we grow older, but it appears to be crucial for healthy aging, balancing inflammation and immune function. A lot remains to be uncovered in this area.
Russ Roberts: That’s fascinating—the gaps in our comprehension. Another intriguing aspect is the role of the gut microbiome; it’s astounding how much we’re still learning about the brain. I often wonder, how did we just now discover this about such a vital organ?
Eric Topol: It is indeed remarkable the number of breakthroughs in brain research we’ve witnessed over the past couple of years.
I’d like to touch on the gut-brain connection, specifically regarding the rising interest in GLP-1 (Glucagon-Like Peptide-1) drugs. Currently, we have a few on the market such as Ozempic and Mounjaro, but this is only the tip of the iceberg. There are ten more gut hormones that we have yet to explore, and their interactions with the brain and immune system are astounding.
For example, GLP-1 drugs are not just effective in reducing appetite; they positively influence eating behaviors, helping people overcome addictions to smoking, alcohol, and gambling. This is a surprising development that reveals how interconnected our gut and brain really are. Remarkably, Ozempic’s effects are mediated through the gut-brain axis rather than direct brain interaction.
This represents one of the most significant discoveries, as we are just beginning to understand the potential of these gut hormones to reduce inflammation and modulate immune responses. The future of this research is incredibly promising.
Russ Roberts: You mentioned knocking down inflammation, a recurring theme in your book. Can you discuss its significance and what’s happening there?
Eric Topol: Certainly. As we age, we encounter a phenomenon known as ‘inflammaging.’ This occurs for various reasons, including the accumulation of senescent cells—some of which can be harmful, secreting pro-inflammatory proteins.
As we age, our immune cells also lose functionality, leading to further inflammation. This chronic inflammation is concerning; for instance, when proteins like amyloid and tau misfold in the brain, inflammation exacerbates the situation. Atherosclerosis, which leads to heart attacks, also worsens with inflammation in arterial walls. And when it comes to cancer, an impaired immune system struggles to combat malignant cells effectively.
Russ Roberts: Let’s revisit those GLP-1 drugs like Ozempic. I haven’t followed them closely but would love to lose weight. However, committing to a new medication for life feels risky. I knew they were initially developed for diabetes, but I didn’t realize their potential beyond that.
Eric Topol: You’re right; we missed a significant opportunity over the past 20 years. Initially, GLP-1 drugs were prescribed for diabetes, and the weight loss effects were minimal for those patients. However, those with obesity experienced remarkable weight loss—30, 50, or even 60 pounds. The mechanism remains unclear.
Moreover, these drugs exhibit cardiovascular benefits and reduce liver fat, but intriguingly, we see anti-inflammatory effects even before any noticeable weight loss occurs. This suggests that the drugs provide a dual benefit—reducing fat while modulating inflammation in the body and brain.
As we await results from upcoming Alzheimer’s trials in early 2026, the potential of Ozempic—and similar medications—could be revolutionary.
Russ Roberts: I’m currently trying to learn Hebrew, which is challenging due to its different characters. It’s a slow process, especially at my age. What strategies do you use to keep up with the ever-evolving medical jargon and discoveries?
Eric Topol: It’s similar to your reading habits, Russ—I read daily, often a couple of hours in the morning before breakfast. I’m hungry for information, whether it’s strictly medical or tangentially related topics like AI.
Evenings often find me returning to more reading. Staying informed is crucial for me.
Russ Roberts: How do you choose your reading material? Where do you source your information?
Eric Topol: I focus on top-tier medical journals like Nature and Science, which I read weekly. Alongside that, I keep up with daily newspapers and other worthwhile books. Reading is not merely a pastime for me; it’s an essential part of my daily routine.
Russ Roberts: I’ve struggled with sleep for the past four years, particularly after moving to Israel and adjusting to a new lifestyle. I typically get only five to six hours a night. Your book emphasizes that poor sleep can lead to long-term health issues. Can you elaborate on the importance of sleep?
Eric Topol: Absolutely! Recent research highlights the crucial role of sleep, particularly the regularity of sleep patterns. Establishing a consistent bedtime is vital, as irregular sleep can increase the risk of dementia and cardiovascular problems.
Another breakthrough relates to what happens during sleep in terms of clearing metabolic waste from the brain. This process, facilitated by the glymphatic system, is particularly effective during deep sleep, which typically occurs during the first few hours of sleep. It’s not merely about the total hours of sleep but ensuring you get sufficient deep sleep.
Maintaining a healthy lifestyle, including proper hydration and avoiding late-night eating or excessive physical activity, can significantly influence sleep quality. We’ve only begun to understand these connections.
Russ Roberts: I want to discuss something that intrigues me. I’ve been advised to take vitamin D supplements due to my deficiency. My concern, though, is whether artificially raising my vitamin D levels will genuinely improve my health outcomes, or if natural sunlight exposure would be more beneficial despite its associated risks. What are your thoughts?
Eric Topol: You’ve made an excellent point. Simply raising vitamin D levels through supplementation doesn’t automatically translate to improved health outcomes. In fact, studies have yet to conclusively prove that increased vitamin D levels lead to reduced osteoporosis or lower all-cause mortality rates.
Similarly, sleep aids like Ambien may provide the illusion of restful sleep, but they hinder the elimination of harmful waste products, potentially worsening overall health. We are only beginning to appreciate these nuances.
Russ Roberts: As a side note, I received several doses of the COVID vaccine, but I decided against taking additional boosters. Given my low-risk status and previous COVID infection, I felt it wasn’t necessary. Some have criticized my decision as politically motivated, but I prioritize evaluating health risks based on personal circumstances. What are your thoughts on this approach?
Eric Topol: Your approach is reasonable, especially since you’ve had three vaccine doses and a COVID infection. Those over 65 should consider the risks associated with additional shots, particularly if they have comorbidities or haven’t previously contracted COVID.
However, it’s essential to understand that waning immunity complicates the situation as new variants emerge. The decision to get vaccinated should be tailored to individual circumstances, especially given the ongoing evolution of the virus.
Russ Roberts: What exactly is a polygenic risk score, and why should we care?
Eric Topol: A polygenic risk score is critical as it takes into account the numerous genetic variants we inherit from our parents that influence our risk for diseases. By analyzing these variants, we can gauge the likelihood of developing conditions like heart disease or cancer.
While not infallible, these scores provide valuable insights into our risk profiles, allowing for more personalized medical decisions. For instance, if your score indicates high risk for heart disease, it may be prudent to consider preventive measures like statin therapy.
Russ Roberts: I’ve heard concerns regarding the anxiety that might arise from receiving such risk assessments. If I discover I have a high risk score for a condition, how do I cope with that information? What actionable steps can I take?
Eric Topol: You’ve touched on an important issue. The challenge lies in translating knowledge of genetic risk into actionable health strategies. For example, if someone has a high polygenic risk score for prostate cancer, they may need more frequent evaluations than someone with a low risk score.
Moreover, lifestyle changes become crucial. When individuals are made aware of their specific risks, they are often more motivated to adopt healthier habits. The key is personalized risk management rather than a one-size-fits-all approach.
