<p><a href="https://peterattiamd.com/briankennedy/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=250721-pod-briankennedy&utm_content=250721-pod-briankennedy-podfeed"> View the Show Notes Page for This Episode</a></p> <p><a href="https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=250721-pod-briankennedy&utm_content=250721-pod-briankennedy-podfeed"> Become a Member to Receive Exclusive Content</a></p> <p><a href="https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=250721-pod-briankennedy&utm_content=250721-pod-briankennedy-podfeed"> Sign Up to Receive Peter's Weekly Newsletter</a></p> <p>Brian Kennedy is a renowned biologist, leader in aging research, and director of the Center for Healthy Longevity at the National University of Singapore. In this episode, Brian shares insights from ongoing human aging studies, including clinical trials of rapamycin and how dosing strategies, timing, and exercise may influence outcomes. He presents two key models of aging—one as a linear accumulation of biological decline and the other as an exponential rise in mortality risk—and explains why traditional models of aging fall short. He also explains why most current aging biomarkers lack clinical utility and describes how his team is working to develop a more actionable biological clock. Additional topics include the potential of compounds like alpha-ketoglutarate, urolithin A, and NAD boosters, along with how lifestyle interventions—such as VO2 max training, strength building, and the use of GLP-1 and SGLT2 drugs—may contribute to longer, healthier lives.</p> <p><strong>We discuss:</strong></p> <ul type="disc"> <li>Brian's journey from the Buck Institute to Singapore, and the global evolution of aging research [2:45];</li> <li>Rethinking the biology of aging: why models like the hallmarks of aging fall short [9:45];</li> <li>How inflammation and mTOR signaling may play a central, causal role in aging [14:15];</li> <li>The biological role of mTOR in aging, and the potential of rapamycin to slow aging and enhance immune resilience [17:30];</li> <li>Aging as a linear decline in resilience overlaid with non-linear health fluctuations [22:30];</li> <li>Speculating on the future of longevity: slowing biological aging through noise reduction and reprogramming [33:30];</li> <li>Evaluating the role of the epigenome in aging, and the limits of methylation clocks [39:00];</li> <li>Balancing the quest for immortality with the urgent need to improve late-life healthspan [43:00];</li> <li>Comparing the big 4 chronic diseases: which are the most inevitable and modifiable? [47:15];</li> <li>Exploring potential benefits of rapamycin: how Brian is testing this and other interventions in humans [51:45];</li> <li>Testing alpha-ketoglutarate (AKG) for healthspan benefits in aging [1:01:45];</li> <li>Exploring urolithin A's potential to enhance mitochondrial health, reduce frailty, and slow aging [1:05:30];</li> <li>The potential of sublingual NAD for longevity, and the combination of NAD and AKG for metabolic and exercise enhancement [1:09:00];</li> <li>Other interventions that may promote longevity: spermidine, 17𝛼-estradiol, HRT, and more [1:17:00];</li> <li>Biological aging clocks, clinical biomarkers, and a new path to proactive longevity care [1:23:15];</li> <li>Evaluating rapamycin, metformin, and GLP-1s for longevity in healthy individuals [1:32:15];</li> <li>Why muscle, strength, and fitness are the strongest predictors of healthspan [1:37:30];</li> <li>Why combining too many longevity interventions may backfire [1:39:30];</li> <li>How increased funding and AI integration could accelerate breakthroughs in aging research [1:41:45];</li> <li>The research Brian is most excited about, and the need to balance innovation with safety in longevity clinics [1:47:00];</li> <li>Peter's reflections on emerging interventions and the promise of combining proven aging compounds [1:54:00]; and</li> <li>More.</li> </ul> <p>Connect With Peter on <a href="https://twitter.com/PeterAttiaMD">Twitter</a>, <a href="https://www.instagram.com/peterattiamd/">Instagram</a>, <a href="https://www.facebook.com/peterattiamd/">Facebook</a> and <a href="https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg">YouTube</a></p>
Actionable Insights
1. Prioritize VO2 Max, Muscle, Strength
Focus on achieving and maintaining high VO2 max, significant muscle mass, and overall strength. These factors profoundly reduce mortality risk, potentially more than avoiding other major health risks like smoking or diabetes.
2. Aggressively Manage Pre-conditions Early
Be proactive in managing early signs of metabolic and cardiovascular diseases, even if slightly outside conventional ‘healthy’ ranges. Early optimization through medication or lifestyle changes can lower biological age and extend lifespan.
3. Understand Aging as Resilience
Frame aging as a process where the body’s resilience, or ability to return to a healthy state after stressors, gradually declines. The goal of interventions should be to maintain or improve this resilience, keeping the ‘hills’ of health higher.
4. Focus on Homeostasis, Not Hallmarks
Avoid viewing aging as a collection of isolated ‘hallmarks’ to be fixed individually. Instead, concentrate on maintaining and improving the body’s overall homeostatic network and its inherent capacity for healthy function.
5. Break mTOR-Inflammation Feedback Loop
Recognize that chronic, low-grade inflammation and elevated baseline mTOR signaling create a destructive feedback loop in aging. Interventions should aim to restore the dynamic range of mTOR and dampen chronic inflammation.
6. Avoid Excessive Intervention Combinations
Exercise caution when combining many different longevity interventions (e.g., 20 pills), as they are more likely to cancel each other out or produce unpredictable, potentially negative outcomes rather than synergistic benefits.
7. Measure Personal Intervention Effects
When experimenting with new interventions, try one or two at a time, carefully observe your body’s response, and use simple measures to track effects. This approach helps identify what works for you and prevents confounding results.
8. Empower Self in Health Decisions
Actively educate yourself about health and longevity interventions, understanding their benefits, risks, and uncertainties. This informed approach allows for better personal health decisions and improved compliance.
9. Reconsider HRT for Women
For women, shift the perspective on Hormone Replacement Therapy (HRT) from ‘should I do it?’ to ‘is there any reason I shouldn’t?’. The value of hormone replacement is believed to significantly outweigh the risks for the majority of women.
10. Optimize Healthspan, Not Max Lifespan
Understand that current longevity interventions primarily improve healthspan (quality of life in later years), potentially adding 5-10 years of healthy life. They are less likely to fundamentally alter maximum human lifespan to extreme ages like 150 or 200.
11. Intermittent Rapamycin Dosing
If considering rapamycin for longevity, opt for an intermittent dosing regimen, such as once a week, allowing trough levels to come down. This approach is less likely to cause immune suppression compared to daily high doses.
12. Time Rapamycin Around Exercise
If using rapamycin, consider timing its intake to avoid hard exercise within 24 hours, as it might acutely impair performance. Optimal training might occur three to four days after taking rapamycin, suggesting a restored dynamic range.
13. Use Clinical Chemistry for Biologic Age
Utilize a comprehensive panel of standard clinical chemistry markers (e.g., from a complete blood count and routine metabolic panel) to derive an actionable biological age assessment. This approach provides insights into modifiable factors and suggests solutions for improvement.
14. Consider Time-Release AKG Supplementation
Explore supplementing with time-release Alpha-Ketoglutarate (AKG), potentially combined with Vitamin A (for males), as it has shown to increase lifespan and dramatically decrease frailty in mice. Time-release is crucial for its efficacy.
Investigate sublingual NAD supplementation, especially when combined with apigenin (a CD38 inhibitor), as this delivery method bypasses digestion and may acutely enhance exercise performance by increasing NAD levels.
Consider spermidine as a robust molecule that may suppress metabolic dysfunction and extend lifespan, particularly in contexts of metabolic challenge, based on mouse data.
17. Urolithin A for Mitochondrial Health
Explore urolithin A, which has shown promise in reducing frailty in male mice and is believed to enhance mitochondrial turnover (mitophagy) and biogenesis, contributing to mitochondrial health.
For individuals who are not perfectly metabolically healthy, SGLT2 inhibitors and GLP-1 agonists may offer benefits beyond their traditional use. These drug classes can optimize metabolic health and potentially contribute to geroprotection.
19. Avoid Unproven Gene/Stem Cell Therapies
Exercise extreme caution with unproven interventions like gene therapy (e.g., folistatin) and questionable stem cell therapies. These carry significant safety concerns and lack efficacy data, especially when offered by unregulated practitioners.
20. Distrust Commercial Biologic Age Tests
Be skeptical of commercial biological age tests, as many lack standardization and reliability. Different tests, and even duplicate runs of the same test, often yield inconsistent results.
21. Deepen Longevity Knowledge
Consider subscribing to resources like Peter Attia’s premium membership to deepen your understanding of health and wellness. This provides access to exclusive content and helps stay informed on the science of longevity.