#333 ‒ Longevity roundtable — the science of aging, geroprotective molecules, lifestyle interventions, challenges in research, and more | Steven Austad, Matt Kaeberlein, Richard Miller
Jan 27, 2025
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In this enlightening discussion, aging experts Steven Austad, Richard Miller, and Matt Kaeberlein delve into the science of aging. They explore the connection between healthspan and lifespan, emphasizing effective interventions like rapamycin and senolytics. The panel critiques the funding challenges in aging research and advocates for more focus on geroscience. Additionally, they examine the complexities of biological age measurements and the potential of GLP-1 receptor agonists in promoting longevity. Packed with humor, insights, and scientific rigor, this conversation is a must-listen!
The podcast emphasizes the growing public interest in longevity science, particularly in understanding the distinction between healthspan and lifespan.
Experts argue for a shift in medical research focus from disease-specific models to a more integrated approach centered on aging.
The discussion raises concerns about underfunding in aging research, advocating for increased investment to align priorities with the significant stakes involved.
Participants express cautious optimism about the potential of metformin and SGLT2 inhibitors for promoting healthy aging, highlighting the need for rigorous studies.
The conversation underscores the importance of interdisciplinary collaboration in longevity research to foster innovative approaches to understanding aging biology.
Deep dives
Importance of Longevity Science
The discussion emphasizes the rising public interest in longevity science, particularly in the concept of healthspan versus lifespan. Experts note that the increased attention may be attributed to a combination of aging populations recognizing their mortality and new technological interests in extending healthy living. The notion that longevity should focus on enhancing quality of life rather than merely prolonging frailty in elderly individuals is also highlighted. This shift has encouraged a more nuanced exploration of what it means to maintain a long, healthy life.
Healthspan vs. Lifespan
The dialogue highlights the critical distinction between healthspan—the period during which an individual is healthy—and lifespan, which merely denotes how long a person lives. Experts stress that these concepts are interlinked, questioning the common belief that improving one requires sacrificing the other. They advocate for research that underscores the importance of both extending the number of healthy years and the total number of years lived. Misconceptions about these terms have underscored the necessity for better education on aging and wellness.
The Role of Epigenetic Changes
Epigenetic changes are examined in relation to aging, with the discussion assessing their potential causal role in the biological aging process. The panel debates whether such changes can be targeted by drugs to reverse or slow aging. While some participants advocate for the significance of epigenetics in aging, others point out the necessity to dive deeper into understanding various cell types and conditions affecting biological mechanisms. This multifaceted inquiry uncovers the complexity and unpredictability of aging processes.
Challenges in Aging Research Funding
The funding landscape for aging research remains a significant topic of concern, with critiques about how government bodies allocate resources. Despite the crucial stakes associated with understanding and treating aging, only a small percentage of NIH funding goes to aging research due to competition from more established fields like cancer and cardiology. Advocates argue that increasing investment in aging research could yield substantial long-term healthcare savings. They call for a realignment of priorities toward foundational aging studies rather than disease-specific funding.
Evaluating Drug Interventions
The discussion on metformin indicates a cautious optimism about its potential to promote healthy aging. Past studies have suggested correlations between metformin use and reduced disease prevalence among older adults. However, these findings are complicated by confounding factors and lack of rigorous trial evidence specifically targeting longevity. Participants suggest that while metformin's preliminary evaluation shows promise, conclusive evidence for its efficacy as a geroprotective agent remains elusive.
The Impact of Exercise on Aging
Exercise is lauded as a key intervention for improving healthspan despite ongoing debates about its direct relationship with aging rates. Experts suggest that the benefits of exercise go beyond just physical improvements, potentially influencing biochemical pathways relevant to aging. They also highlight the complexities of exercise regimens and their varying effects based on intensity, consistency, and type. This exploration advocates for recognizing exercise as a multifactorial intervention that affects countless variables linked to aging.
Insights on SGLT2 Inhibitors
The conversation shifts to SGLT2 inhibitors like canagliflozin, which have shown promising benefits for health and longevity in preclinical trials. These drugs appear to affect metabolic health and have implications for preventing age-related diseases. Participants highlight the need for more comprehensive studies to elucidate their mechanisms of action in both animal models and humans. The discussion suggests that optimizing the timing and method of administration could amplify their benefits further.
Senescent Cells and Aging
The role of senescent cells in aging is critically analyzed, with differing opinions on their impact and the validity of targeting them. The conversation discusses whether the accumulation of senescent cells drives the aging process or if they are a mere byproduct of it. While some believe that targeting these cells can enhance healthspan, skeptics caution against generalizing findings from specific cell types to the broader aging process. Ultimately, the experts agree on the need for rigorous research to clarify the implications of senescent cells for aging and health.
Future Directions in Longevity Research
The contributors to the discussion express optimism about future developments in longevity science, highlighting opportunities for breakthroughs in grasping the biology of aging more fully. By focusing on both genetic and lifestyle factors, researchers aim to discern effective interventions that can promote healthier aging. The dialogue stresses the importance of integrating methodologies to study the interactions between various biological systems implicated in aging. These collective efforts could lead to novel therapeutic strategies for age-related diseases.
Interdisciplinary Approaches to Aging
Experts highlight the value of interdisciplinary approaches to addressing aging, suggesting that collaboration across fields can lead to more holistic understandings. The conversation points to potential synergies between geroscience, endocrinology, immunology, and neurology, among others. Engaging diverse specialties enables a comprehensive examination of feedback loops and biological networks that contribute to aging. This cross-disciplinary environment can drive the innovations necessary for targeting aging on multiple fronts simultaneously.
In this special episode of The Drive, Peter introduces a brand-new roundtable format. Joined by three renowned experts in longevity science—Steven Austad, Richard Miller, and Matt Kaeberlein—the group explores the rapidly evolving field of geroscience. Together, they dive deep into topics like the relationship between healthspan and lifespan, evaluating interventions like rapamycin and senolytics, the role of epigenetic changes in aging, and whether GLP-1 receptor agonists hold geroprotective potential. They also tackle major challenges in funding and public acceptance of longevity research including how geroprotective interventions might be tested in humans. Packed with nuanced debate, humor, and groundbreaking insights, this episode is a must-listen for anyone fascinated by the science of aging.
We discuss:
The recent rise in public interest in longevity, misconceptions, and the link between healthspan and lifespan [3:45];
Redefining healthspan, the US healthcare paradox, and separating longevity science from commercial hype [12:30];
The need to redirect medical research from disease-specific models to aging-focused approaches [21:30];
Proactive healthcare: rethinking health, disease, and the role of aging [30:00];
Biologic age versus chronologic age, and the limitations and potential of epigenetic clocks [35:00];
The utility and drawbacks of the “hallmarks of aging” as a framework for research and funding [49:30];
The role of epigenetic changes in aging and the challenges of proving causality [56:45];
The translational challenges of moving aging research from preclinical studies to human applications [1:03:45];
Distinguishing between a biomarker of aging and aging rate indicators [1:17:15];
The difficulties of translating longevity research in mice to humans, and the difficulties of testing interventions in humans [1:21:15];
Exercise, aging, and healthspan: does exercise slow aging? [1:35:45];
Are GLP-1 receptor agonists geroprotective beyond caloric restriction effects? [1:41:00];
The role of senescent cells in aging, challenges with reproducibility in studies, and differing views on the value of current research approaches [1:46:15];
How funding challenges and leadership in NIH and other institutes impact the advancement of aging-related research [2:00:15];
Metformin: geroprotective potential, mechanisms, and unanswered questions [2:02:30];
Canagliflozin and rapamycin as geroprotective molecules: mechanisms, dosing strategies, and longevity potential [2:10:45];
Resveratrol and NAD precursors—a lack of evidence for anti-aging effects [2:22:45];
The potential of parabiosis and plasmapheresis to slow aging, the challenges in translating mouse studies to humans, and possible design for human studies [2:29:45]; and
